From ApoE4.Info Wiki
Jump to: navigation, search

What is BDNF?

Brain Derived Neurotrophic Factor is a protein produced by neurons and regulates synaptic transmission in the hippocampus. It promotes neurogenesis and nerve growth. Because it plays a critical role in neuronal survival, synaptic plasticity, and memory, BDNF reduction may contribute to synaptic and cellular loss and memory deficits characteristic of Alzheimer’s Disease. BDNF serum values increase in the early stages of AD, which might reflect compensatory repair; however, it decreases as the disease progresses. BDNF might also explain some of the increased risk of AD in women.


BDNF and synaptic plasticity, cognitive function, and dysfunction. (2014, Abstract)

Converging evidence now strongly suggest that deficits in BDNF signaling contribute to the pathogenesis of several major diseases and disorders such as Huntington's disease, Alzheimer's disease, and depression. Thus, manipulating BDNF pathways represents a viable treatment approach to a variety of neurological and psychiatric disorders.

Brain Derived Neurotrophic Factor: a novel neurotrophin involved in psychiatric and neurological disorders. (2012, Abstract)

BDNF may be the "missing-link" that mediates the interaction between gene and environment, synaptic plasticity and apoptosis and transgenerational transmission of disease vulnerability. There is theoretical and empirical support for a model in which BDNF underpins the integrity of the central nervous system and this may herald a quantum leap in the way we approach disorders of the mind and brain. Understanding and developing therapies centered on the role of BDNF may lead to paradigm shifts in current practice and treatment of psychiatric and neurological disorders.

Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia (2014, Full text)

Brain-derived neurotrophic factor (BDNF) may explain some of the variation in dementia risk. Because it is inducible by factors such as reduced caloric intake and increased physical activity, it is thought to mediate the association between healthy lifestyle and successful aging. In animal models, BDNF is highly expressed and widely distributed throughout the central nervous system especially in the hippocampus and cerebral cortex and is important in the survival and function of hippocampal and cortical, as well as cholinergic and dopaminergic, neurons. In addition, BDNF is critical for synaptic plasticity and memory processing in the adult brain.


The effects of genetics - it’s complicated...

The most commonly studied BDNF variant is rs6265 val66met. The more common G allele encodes the Val, while the A allele encodes Met.

BDNF val66met polymorphism affects aging of multiple types of memory. (2014, Abstract)

The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating that the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (p<.07) toward poorer associative memory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory).

Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia (2014, Full text)

The absence of a significant association between BDNF SNPs and the risk for AD is not inconsistent with the association we show between serum BDNF levels and the risk for AD in women since genetic variation does not appear to explain a substantial proportion of the variation in BDNF levels. Rather, environmental factors, such as mood, diet, and physical activity likely alter BDNF levels. BDNF may be a biological intermediate between these lifestyle factors and their impact of AD pathology and risk, a hypothesis that needs further exploration in additional studies.


Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism (2013, Full text)

Although the val66met polymorphism does not seem to affect the activity of mature BDNF, the intracellular trafficking and activity-dependent secretion of BDNF is altered (Egan et al., 2003). At a cellular level, there appears to be a met-dose effect on intracellular localisation (Chen et al., 2004) and regulation of activity-dependent secretion of BDNF (Chen et al., 2006). Variations in n-acetyl-aspartate (NAA) levels in the hippocampus associated with the met-allele also suggest a functional met-dose effect (Egan et al., 2003).

Hippocampal investigations in BDNF are legion, and most commonly indicate a met-effect of reduced hippocampal volume (Pezawas et al., 2004), although these changes are not consistent (Koolschijn et al., 2010; Toro et al., 2009), and have recently been suggested to be artificial due to a “winners curse” (Molendijk et al., 2012). In our analysis we did not detect an effect of genotype in the hippocampus.

Common across all our findings is the “U-shaped” profile, where heterozygotes are distinct from the homozygotes. Given our relative lack of insight into the biology of the BDNF met-allele, as well as a dearth of studies examining the met-dose effect on brain structure, it is yet too early to know how to interpret these changes. However it does offer the important insight that, by grouping all met-carriers together, previous quantitative investigations may have missed an important aspect of the interaction between the met and val alleles.

Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer's disease neurodegeneration. (2013, Full text)

There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF), may impact aging and Alzheimer's Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs) impact Alzheimer's Disease-related brain imaging and cognitive markers of disease.

Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108). No SNPs were significantly associated with baseline brain volume measures; however, six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850). We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume.

Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks (2011, Full text)

Taken together, converging results from both item and relational memory tasks suggest that the increase in hippocampal and parahippocampal gyrus activation for BDNF met allele carriers is not simply associated with task-related processing, but rather successful memory performance. The findings were strikingly similar across both encoding and retrieval stages of memory processing. These results indicate that met carriers are able to recruit MTL activity in order to support equitable memory performance. Moreover, reductions in cognitive performance are not a ubiquitous effect associated with the BDNF val66met genotype of these individuals or group differences in MTL volume. These findings combined with that of previous studies also underscore the variability in results across fMRI studies attempting to measure complex cognitive functioning.

Gender-related association of brain-derived neurotrophic factor gene 196A/G polymorphism with Alzheimer's disease-a meta-analysis including 6854 cases and 6868 controls. (2014, Abstract)

Epidemiological studies have evaluated the associations between brain-derived neurotrophic factor (BDNF) 196A/G gene polymorphism and Alzheimer's disease (AD) risk. However, the results remain inconclusive. Sexually dimorphic effect of the polymorphism of BDNF 196A/G in AD patients had been proposed previously, specifically in female group. As more cases were reported, therefore, we performed a meta-analysis of published case-control studies to better understand these results. We systematically searched online databases of Embase, PubMed, and Web of Science, as well as hand searching of the references of identified articles and meeting abstracts. Review Manager (Version 5.2.4) and Stata software (Version 12.0) were used for statistical analyses. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. A total of 23 publications including 25 studies were identified and entered the analysis. No significant association was observed in overall population, as well as subgroups stratified by ethnicity (Caucasian and Asian). However, when stratified by gender, significant association was observed just in female subgroup (A allele vs. G allele: OR = 1.15, 95% CI = 1.06-1.25; A/A vs. G/G: OR = 1.29, 95% CI = 1.06-1.57; A/A + A/G vs. G/G: OR = 1.30, 95% CI = 1.11-1.53). This meta-analysis confirmed the gender-related association between BDNF 196A/G polymorphism and AD risk, which may indicate a certain effect of female hormone on progression of the disease. Larger sample size and more studies with homogeneous AD patients and well-matched controls are needed in the future.

Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta-analysis. (2010, Abstract)

Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (BDNF) confer susceptibility to Alzheimer's disease (AD). We genotyped these polymorphisms in a Japanese sample of 657 patients with AD and 525 controls, and obtained weak evidence of association for Val66Met (P = 0.063), but not for C270T. After stratification by sex, we found a significant allelic association between Val66Met and AD in women (P = 0.017), but not in men. To confirm these observations, we collected genotyping data for each sex from 16 research centers worldwide (4,711 patients and 4,537 controls in total). The meta-analysis revealed that there was a clear sex difference in the allelic association; the Met66 allele confers susceptibility to AD in women (odds ratio = 1.14, 95% CI 1.05-1.24, P = 0.002), but not in men. Our results provide evidence that the Met66 allele of BDNF has a sexually dimorphic effect on susceptibility to AD.

Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study (2014, Full text)

During follow-up, 140 participants developed dementia, 117 of whom had AD. Controlling for age and sex, each standard-deviation increment in BDNF was associated with a 33% lower risk for dementia and AD (P = .006 and P = .01, respectively). These associations persisted after additional adjustments. Compared with the bottom quintile, BDNF levels in the top quintile were associated with less than half the risk for dementia and AD (hazard ratio, 0.49; 95%CI, 0.28–0.85; P = .01; and hazard ratio, 0.46; 95%CI, 0.24–0.86; P = .02, respectively). These associations were apparent only among women, persons aged 80 years and older, and those with college degrees (hazard ratios for AD: 0.65, [95%CI, 0.50–0.85], P = .001; 0.63 [95%CI, 0.47–0.85], P = .002; and 0.27 [95%CI, 0.11–0.65], P = .003, respectively). Brain-derived neurotrophic factor genetic variants were not associated with AD risk.


Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. (2014, Abstract)

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults.The present results suggest that aging is an important factor related to decline in BDNF level.

Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders. (2014, Abstract)

A history of childhood trauma or being a met carrier of the BDNF val66met was associated with significantly reduced BDNF mRNA level. Additive effects were observed between a history of childhood trauma and BDNF val66met, in the direction of met carriers with high levels of childhood trauma having the lowest BDNF mRNA levels. Lastly, met carriers reporting high levels of childhood trauma (specifically sexual or physical abuse) had significantly reduced hippocampal subfield volumes CA2/3 and CA4 dentate gyrus.

Apathy and APOE4 are associated with Reduced BDNF Levels in Alzheimer's Disease. (2014, Abstract)

These results show the association of apathy and APOE4 with reduced serum BDNF levels in AD, and suggest that BDNF reductions might contribute to the worse cognitive performance exhibited by AD apathetic patients and female APOE4 carriers.

Proposed mechanism(s)

BDNF mediates adaptive brain and body responses to energetic challenges. (2014, Abstract)

By stimulating glucose transport and mitochondrial biogenesis, BDNF bolsters cellular bioenergetics and protects neurons against injury and disease. By acting in the brain and periphery, BDNF increases insulin sensitivity and parasympathetic tone. Genetic factors, a 'couch potato' lifestyle, and chronic stress impair BDNF signaling, and this may contribute to the pathogenesis of metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes, and neurological disorders.

Amyloid-β oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons. (2013, Full text)

Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-β oligomers (AβOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AβOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AβOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3β, downstream targets of CaN, prevents BDNF transport defects induced by AβOs. We further show that AβOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AβO-induced BDNF transport disruption.

Dysregulation of Neurotrophic and Haematopoietic Growth Factors in Alzheimer’s Disease: From Pathophysiology to Novel Treatment Strategies (2014, Full text) - click on download to see full article

But may not be a good marker to test on its own

Neuroinflammation and Brain Functional Disconnection in Alzheimer’s Disease (2013, Full text)

Activated T lymphocytes can nevertheless also mediate neuroprotection and promote neurogenesis by secreting BDNF. BDNF production was increased in aMCI; these results are in line with data showing higher BDNF serum levels in preclinical stages of Alzheimer’s disease (Laske et al., 2006; Angelucci et al., 2010) and with post-mortem examinations of AD brains indicating a significant increase of BDNF concentration in hippocampus and parietal cortex (Durany et al., 2000) and of its receptor TrkB in astrocytes and senile plaques (Connor et al., 1997).

The Associations between Serum Brain-Derived Neurotrophic Factor, Potential Confounders, and Cognitive Decline: A Longitudinal Study (2014, Full text)

Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline.

Related SNPs / APOE4 Effects

Associations Between ApoEε4 Carrier Status and Serum BDNF Levels-New Insights into the Molecular Mechanism of ApoEε4 Actions in Alzheimer's Disease. (2014, Abstract)

Insufficient neurotrophic support increases the risk for developing Alzheimer's disease (AD). Mounting evidence has confirmed the association of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) with AD. As both BDNF and ApoE are suggested to be involved in modulating brain integrity, the present study is aiming to investigate the associations between these two factors. We further found that ApoE ε4+/- and ε4+/+ subjects had significantly lower serum BDNF levels than ε4-/- subjects in the whole cohort and the NC group, suggesting altered BDNF metabolism in ApoE ε4 carriers.

Association of rs6265 and rs2030324 Polymorphisms in Brain-Derived Neurotrophic Factor Gene with Alzheimer’s Disease: A Meta-Analysis (2014, Full text)

This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD.

APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease. (2014, Abstract)

Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4-/BDNFVal/Val participants (d=0.90-1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years.

See also:

Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein E ε4 carriers. (2013, Full text)

APOE and COMT polymorphisms are complementary biomarkers of status, stability, and transitions in normal aging and early mild cognitive impairment (2014, Full text)

For BDNF, Met carriers (both A/A and A/G) are at risk.

The other polymorphism (BDNF) was not statistically associated with the targeted outcomes. In general, BDNF-cognition associations are inconsistently observed and difficult to interpret (Mandelman & Grigorenko, 2012). In addition, BDNF associations are rarely tested as predictors of clinical or cognitive status or neurodegenerative changes (cf. Forlenza et al., 2010). The mechanisms through which BDNF may affect neurocognitive performance are proposed (Savitz et al., 2006; Harris and Deary, 2011) but their relevance to non-normal cognitive status has not been firmly established. As an MCI predictor, BDNF may be less relevant for early classification (as in this study) than for later cognitive impairment (Forlenza et al., 2010). We included BDNF for two reasons: (a) it could have been related to objective cognitive status as we assess it (via performance on a reference battery including memory and speed markers) and (b) it could have appeared as an associate of cognitive status in the role of interacting influence.

APOE and BDNF Val66Met polymorphisms combine to influence episodic memory function in older adults. (2014, Abstract)

Our data show that concurrent consideration of both APOE and BDNF polymorphisms are required in order to witness a cognitive effect in healthy older adults.


Increasing BDNF can ameliorate amyloid β-induced neuronal damage in our mouse friends. (Abstract)

Brain-derived neurotrophic factor: from nerve growth factor to modulator of brain plasticity in cognitive processes and psychiatric diseases (2006, [1])

In the brain and serum, BDNF is modulated by different factors. It is downregulated by stress and upregulated by learning processes, several antidepressive treatments, physical activity, and dietary restriction.

Diet and Gut Health is important

Gut Bacteria Might Guide The Workings Of Our Minds (Article from NPR, Full text)

But other researchers have been trying to figure out a possible connection by looking at gut microbes in mice. There they've found changes in both brain chemistry and behavior. One experiment involved replacing the gut bacteria of anxious mice with bacteria from fearless mice.

"The mice became less anxious, more gregarious," says Stephen Collins of McMaster University in Hamilton, Ontario, who led a team that conducted the research.

It worked the other way around, too — bold mice became timid when they got the microbes of anxious ones. And aggressive mice calmed down when the scientists altered their microbes by changing their diet, feeding them probiotics or dosing them with antibiotics.

To find out what might be causing the behavior changes, Collins and his colleagues then measured brain chemistry in mice. They found changes in a part of the brain involved in emotion and mood, including increases in a chemical called brain-derived neurotrophic factor, which plays a role in learning and memory. A big nerve known as the vagus nerve, which runs all the way from the brain to the abdomen, was a prime suspect. And when researchers in Ireland cut the vagus nerve in mice, they no longer saw the brain respond to changes in the gut.

"The vagus nerve is the highway of communication between what's going on in the gut and what's going on in the brain," says John Cryan of the University College Cork in Ireland, who has collaborated with Collins.

Gut microbes may also communicate with the brain in other ways, scientists say, by modulating the immune system or by producing their own versions of neurotransmitters.

"I'm actually seeing new neurochemicals that have not been described before being produced by certain bacteria," says Mark Lyte of the Texas Tech University Health Sciences Center in Abilene, who studies how microbes affect the endocrine system. "These bacteria are, in effect, mind-altering microorganisms."

An abstract of Collins research is available: The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications (Abstract)

Combination of apolipoprotein E4 and high carbohydrate diet reduces hippocampal BDNF and arc levels and impairs memory in young mice. (2012, Abstract)

The presence of the E4 allele of apolipoprotein E (apoE) is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD). Other risk factors for developing AD have been identified, including lifestyle such as dietary habits. The present study was designed to explore the impact of the interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning and memory retention. As an investigative model, we compared young apoE3 and apoE4 target replacement mice fed on a HCD for 6 months. Our results indicate that HCD compromises memory processes in apoE4 mice. ApoE4 mice on HCD showed decreased activity-regulated cytoskeletal-associated protein (Arc) and brain derived neurotrophic factor (BDNF) levels, as well as decreased BDNF signaling in the hippocampus. In contrast, apoE3 mice were resistant to the deleterious effects of HCD on both behavior and memory-related proteins. Our results support the hypothesis that already in mid-life, genetic, and environmental risk factors act together on the mechanisms behind cognitive impairment.

And don’t eat too much

Circulating Brain-Derived Neurotrophic Factor Concentration Is Downregulated by Intralipid/Heparin Infusion or High-Fat Meal in Young Healthy Male Subjects (2012, Full text)

Plasma BDNF decreased also by 27.8% in 6 h after a high-fat meal. Our results demonstrate for the first time that 6 h of intralipid/heparin infusion during hyperinsulinemic euglycemic clamp significantly decreased by 43% serum BDNF and by 35% plasma BDNF level."


Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease. (2014, Abstract)

A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

Influence of BDNF Val66Met on the relationship between physical activity and brain volume. (2014, Abstract)

The BDNF Val66Met polymorphism interacted with physical activity to be associated with hippocampal (β = -0.22, p = 0.02) and temporal lobe (β = -0.28, p = 0.003) volumes. In Val/Val homozygotes, higher levels of physical activity were associated with larger hippocampal and temporal lobe volumes, whereas in Met carriers, higher levels of physical activity were associated with smaller temporal lobe volume.

The Effects of Aerobic Exercise Intensity and Duration on Levels of Brain-Derived Neurotrophic Factor in Healthy Men (2013, full text)

Physical exercise caused an average ~ 32% increase in sBDNF levels relative to baseline that resulted in concentrations that were 45% higher than control conditions.

Other Factors

Dysregulation of Neurotrophic and Haematopoietic Growth Factors in Alzheimer’s Disease: From Pathophysiology to Novel Treatment Strategies (2014, Full text) - click on download to see full article

A mouse study showed that when the BDNF gene was delivered with the help of a vector, BDNF postponed synapse loss and improved cell signaling and cognitive functions. It did not affect the number of neurons or the amyloid load, showing that BDNF does not directly interact with beta-amyloid.


We found that progesterone does indeed elicit an increase in both BDNF protein and mRNA levels in the cerebral cortex.

Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment. (2016, Abstract)

Sleep disorders negatively affect cognition and health. Recent evidence has indicated that chromatin remodeling via histone acetylation regulates cognitive function. This study aimed to investigate the possible roles of histone acetylation in sleep deprivation (SD)-induced cognitive impairment. Furthermore, sleep deprivation can reduce H3 and H4 acetylation levels in the promoters of the brain-derived neurotrophic factor (BDNF) gene and thus significantly downregulate BDNF expression and impair the activity of key BDNF signaling pathways (pCaMKII, pErk2, and pCREB).

BDNF and its histone acetylation regulation may play important roles in SD-induced spatial memory impairment, whereas HDAC inhibition possibly confers protection against SD-induced impairment in spatial memory and hippocampal functions.


Serum Brain-Derived Neurotrophic Factor Levels in Different Neurological Diseases (2013, Full text)

Analyses of potential modulatory effects of pharmacological treatments (Table 2, Figure 2) on BDNF levels in the whole sample of patients taking various common psychiatric medications revealed higher BDNF serum levels in patients treated with mood stabilizers/antiepileptics (P = 0.009) and L-DOPA (P < 0.001) and significant reductions in neurotrophin concentrations in patients treated with benzodiazepines (P = 0.020).


Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease. (2013, Full text)

Procyanidins protect against oxidative damage and cognitive deficits after traumatic brain injury. (2014, Abstract)

About Procyanidins Procyanidins, including the lesser bioactive / bioavailable polymers (4 or more catechines) represent a group of condensed flavan-3-ols that can be found in many plants, most notably apples, maritime pine bark, cinnamon, aronia fruit, cocoa beans, grape seed, grape skin,[1] and red wines of Vitis vinifera (the common grape). However, bilberry, cranberry, black currant, green tea, black tea, and other plants also contain these flavonoids. Cocoa beans contain the highest concentrations.[2] Procyanidins can also be isolated from Quercus petraea and Q. robur heartwood (wine barrel oaks).[3] Açaí oil, obtained from the fruit of the açaí palm (Euterpe oleracea), is rich in numerous procyanidin oligomers.[4]

Apples contain on average per serving about eight times the amount of procyanidin found in wine, with some of the highest amounts found in the Red Delicious and Granny Smith varieties.[5] A patented extract of maritime pine bark called Pycnogenol bears 65-75 percent procyanidins (procyanidins).[6] Thus a 100 mg serving would contain 65 to 75 mg of procyanidins.


Folic acid prevented cognitive impairment in experimental pneumococcal meningitis. (2014, [2] Abstract)

Neuroprotection by Association of Palmitoylethanolamide with Luteolin in Experimental Alzheimer's Disease Models: the Control of Neuroinflammation. (2014, Abstract)


NMDA receptor dysregulation in chronic state: A possible mechanism underlying depression with BDNF downregulation. (2014, Abstract)

Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease. (2014, Abstract)

Epigenetic suppression of hippocampal BDNF mediates the memory deficiency induced by amyloid fibrils. (2014, Abstract)

But, the epigenetic effect might also offer solutions to treatment

Epigenetic regulation of the BDNF gene: implications for psychiatric disorders. (2012, Abstract)

More specifically, various environmental factors, particularly when occurring during development, have been claimed to produce long-lasting epigenetic changes at the BDNF gene, thereby affecting availability and function of the BDNF protein. Such stabile imprints on the BDNF gene might explain, at least in part, the delayed efficacy of treatments as well as the high degree of relapses observed in psychiatric disorders. Moreover, the BDNF gene has a complex structure displaying differential exon regulation and usage, suggesting a subcellular- and brain region-specific distribution. As such, developing drugs that modify epigenetic regulation at specific BDNF exons represents a promising strategy for the treatment of psychiatric disorders.

Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor. (2014, Abstract)

Acupuncture stimulation improves scopolamine-induced cognitive impairment via activation of cholinergic system and regulation of BDNF and CREB expressions in rats. (2014, [ Abstract])

Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease. (2014, Abstract)

Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice. (2014, Abstract) Note: Lamotrigine is an anticonvulsant drug used in epilepsy and bipolar disorder.

Environmental Enrichment Lessens Cognitive Decline in APP23 Mice Without Affecting Brain Sirtuin Expression. (2014, Abstract)

Does Melatonin Ameliorate Neurological Changes Associated With Alzheimer’s Disease in Ovariectomized Rat Model? (2013, Abstract) Note: this study looked at females only

Chinese Herbs & Supplements

Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins. (2014, Full text)

Inhibitory Effects of Eucommia ulmoides Oliv. Bark on Scopolamine-Induced Learning and Memory Deficits in Mice. (2013, Full text)

Rutin activates the MAPK pathway and BDNF gene expression on beta-amyloid induced neurotoxicity in rats. (2014, Abstract)

Panax notoginsenoside Rb1 ameliorates Alzheimer's disease by upregulating brain-derived neurotrophic factor and downregulating Tau protein expression. (2013, Full text)

Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model. (2013, Abstract)

Curcumin produces neuroprotective effects via activating brain-derived neurotrophic factor/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons. (2010, Abstract)

Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers. (2010, Abstract)


BDNF has an important role in neurogenesis, memory, and overall brain health. To boost BDNF levels, exercise, pursue mental challenges, manage stress, eat the good stuff (but not too much, especially sugar), and watch hormonal health (for women).