Pathway of Alzheimer's degeneration discovered

[TheBrain]

https://medicalxpress.com/news/2018-07- ... on.html#ms

Scientists at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University have used a unique approach to track brain degeneration in Alzheimer's disease, uncovering a pathway through which degeneration spreads from one region to another.

Individuals in the early stages of Alzheimer's disease (AD) were scanned using both structural magnetic resonance imaging (sMRI) and positron emission tomography (PET). The scientists were interested in how AD affects the basal forebrain—a deep brain structure that supplies the outer cortex with acetylcholine, a neurotransmitter that is critical for maintaining normal brain function. They found that as cholinergic neurons in the basal forebrain degenerate, the areas in the cortex which receive their cholinergic inputs also degenerate.

[circular]

That is interesting! I wonder how much of the degeneration of the cholinergic neurons in the basal forebrain is due to lack of choline and how much to other factors. I'll have to have a read ...

[circular]

Much of this brief article is interesting:

"A key finding from this study is that the results from sMRI scans matched what we were seeing on PET scans, despite the fact they provide different types of measurements and were performed on different patients" said Dr. Nathan Spreng, Director of the Laboratory of Brain and Cognition at The Neuro. "The combination of PET with sMRI may therefore represent be a powerful tool for tracking the progression of Alzheimer's disease in living patients."

"This study shows PET and sMRI scans could potentially be used to diagnose Alzheimer's disease before cognitive symptoms appear, giving doctors a better window of time to work on prevention," said Taylor Schmitz, researcher in Dr. Spreng's lab and the study's lead author. "Drugs that promote the delivery of acetylcholine to these cortical regions could be one way to prevent degeneration."

[circular]

Full text:

[url=
https://www.cell.com/cell-reports/fullt ... ngitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections[/url]

Sorry link won't behave, I guess due to the parens in the web address?

[slacker]

Full text:

[url=
https://www.cell.com/cell-reports/fullt ... ngitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections[/url]

Sorry link won't behave, I guess due to the parens in the web address?

Is this the link you were trying to post? This is the pdf form.

[ChipW]

"Drugs that promote the delivery of acetylcholine to these cortical regions could be one way to prevent degeneration."

Hum.. i wonder if supplementing with something like alpha gpc would be beneficial?

Sent from my SM-N950U using Tapatalk

[circular]

Hum.. i wonder if supplementing with something like alpha gpc would be beneficial?

I wonder this too. I think they're beneficial in any case for me since I have wonky choline/phosphatidylcholine genetics, but I'm now wondering if such supplements might help forestall this particular process. It may be wishful thinking, since a lot of things can damage neurons.

[circular]

Is this the link you were trying to post? This is the pdf form.

Thanks

[SusanJ]

After reading this, it seems that acetylcholine would only be one variable.

If the cholinergic BF neurons are selectively vulnerable to perturbed energy homeostasis, oxidative stress, and neuroinflammation due to their large axons (Lewis et al., 2010; Mattson and Magnus, 2006; Wang et al., 2010; Wu et al., 2014), they might lose the capacity to maintain full trophic support of these large axons over the course of aging. Lending support to this hypothesis, the number of cholinergic fibers per BF neuron reduces in early middle age, and especially in the transition from preclinical to MCI stages of AD, against a background of accumulating intraneuronal Ab, hyper-phosphorylated Tau, and neurofibrillary tangles (Arendt et al., 2015; Baker-Nigh et al., 2015; Braak and Braak, 1991; Braak and Del Tredici, 2015; Geula et al., 2008; Mesulam et al., 2004; Mesulam, 2013; Schliebs and Arendt, 2006, 2011). As a result, the cortex and amygdalae might become progressively denuded of cholinergic input, with genetic AD risk factors such as the APOE ε4 allele (Poirier et al., 1995) and reduced metabolism (Rivera et al., 2005) contributing to differentiate normal age-related from AD trajectories of cholinergic loss.

And the authors state

Nevertheless, in humans, stronger connections are needed to link the progression of cortical cholinergic denervation to its potentially very early roles in driving cortical neuropathology and altering cortical functions important for cognition, such as selective attention (Romberg et al., 2013; Schmitz et al., 2010, 2014; Schmitz and Duncan, 2018).

Standard T1-weighted sMRI measures of gray matter volume cannot distinguish different cell types. Hence, we cannot infer from our sMRI data alone whether longitudinal reductions in gray matter within the BF reflect a selective loss of cholinergic cell bodies, or some combination of cholinergic, GABAergic, and glutamatergic neurons known to co-populate its MS/DBB and NbM subregions (Henny and Jones, 2008; Lin et al., 2015).

I think it does underscore how important it is to tackle all the things we talk about on the forum, particularly before middle age, by providing the brain appropriate energy sources (metabolic flexibility by reducing IR, ketosis), and controlling oxidative stress and inflammation.

[circular]

Thanks Susan. It's rewarding to see so much research moving in the direction that we would expect if our 'takes' from earlier studies are right.