And the list of studies linking cholesterol and AD goes on and on and on . . . .
Correct ... cholesterol does play a role.
But, cholesterol itself is not the determining factor ... it's cholesterol in a high insulin / high blood sugar environment.
From the link I posted above:
An emerging body of evidence suggests that an increased prevalence of insulin abnormalities and insulin resistance in Alzheimer's disease may contribute to the disease pathophysiology and clinical symptoms. It has long been known that insulin is essential for energy metabolism in the periphery. In the past 2 decades, convergent findings have begun to demonstrate that insulin also plays a role in energy metabolism and other aspects of CNS function. Investigators reported 20 years ago that insulin and insulin receptors were densely but selectively expressed in the brain, including the medial temporal regions that support the formation of memory. It has recently been demonstrated that insulin-sensitive glucose transporters are localised to the same regions supporting memory and that insulin plays a role in memory functions. Collectively, these findings suggest that insulin may contribute to normal cognitive functioning and that insulin abnormalities may exacerbate cognitive impairments, such as those associated with Alzheimer's disease. Insulin may also play a role in regulating the amyloid precursor protein and its derivative beta-amyloid (Abeta), which is associated with senile plaques, a neuropathological hallmark of Alzheimer's disease. It has been proposed that insulin can accelerate the intracellular trafficking of Abeta and interfere with its degradation. These findings are consistent with the notion that insulin abnormalities may potentially influence levels of Abeta in the brains of patients with Alzheimer's disease. The increased occurrence of insulin resistance in Alzheimer's disease and the numerous mechanisms through which insulin may affect clinical and pathological aspects of the disease suggest that improving insulin effectiveness may have therapeutic benefit for patients with Alzheimer's disease. The thiazolidinedione rosiglitazone has been shown to have a potent insulin-sensitising action that appears to be mediated through the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). PPAR-gamma agonists, such as rosiglitazone, also have anti-inflammatory effects that may be of therapeutic benefit in patients with Alzheimer's disease. This review presents evidence suggesting that insulin resistance plays a role in the pathophysiology and clinical symptoms of Alzheimer's disease. Based on this evidence, we propose that treatment of insulin resistance may reduce the risk or retard the development of Alzheimer's disease
And this one ...
Clinically, Alzheimer’s patients present with decreased cognitive function and lapses in memory that decline progressively and ultimately impact performance of everyday life tasks. Physiologically, AD is characterised by several physical hallmarks that can be measured or observed via biopsy, positron emission tomography (PET) scan, or upon autopsy. These include insoluble extracellular plaques made of beta-amyloid peptide (Aβ); intracellular neurofibrillary tangles (NFTs), loss of hippocampal neurons; and a marked decline in the metabolism of glucose in regions of the brain associated with memory and learning. All of these changes can be logically explained as sequelae resulting from long-term dysregulation of insulin signalling and glucose energetics.
A noteworthy feature of AD is the combination of hyperinsulinism in the periphery with hypoinsulinism in the CNS. Patients with advanced AD show higher plasma but lower cerebrospinal fluid (CSF) insulin concentrations than healthy controls and subjects with mild cognitive impairment. Moreover, the ratio of CSF to plasma insulin levels was significantly lower in patients with advanced dementia, with the degree of difference correlating to dementia severity.33 These compartmentalised alterations in insulin concentration were observed in individuals who lacked the strongest currently known genetic risk factor for development of AD: homozygosity for the ε-4 allele of the apolipoprotein E gene (ApoE4). This suggests again that peripheral hyperinsulinaemia/IR is a significant risk factor for AD regardless of genotype.34
The synthesis and secretion of amyloid precursor proteins are normal physiological processes. The formation of the insoluble plaques is what distinguishes an Alzheimer’s brain from a healthy brain. However, there is no evidence that Alzheimer’s patients secrete more Aβ than healthy individuals; rather, in AD patients, these proteins are not properly degraded and cleared away. The enzyme responsible for degrading amyloid proteins in the brain is insulysin, also known as insulin degrading enzyme (IDE) – the same enzyme tasked with degrading insulin (as well as glucagon, atrial natriuretic peptide, and more). Peripheral hyperinsulinaemia – as seen in T2D, metabolic syndrome and other hyperinsulinaemic conditions associated with greater risk for AD – may induce a functional deficiency of IDE.40 The affinity of IDE for insulin is much greater than that for Aβ, such that the presence of even small amounts of insulin completely inhibits the degradation of Aβ.38,40 Thus, when IDE is saturated with insulin as a substrate, Aβ is left to accumulate and form plaques.
Finally, it is crucial to address the strongest and, to date, only known genetic risk factor for Alzheimer’s disease: possession of one or two ε4 (E4) alleles of the APOE gene (ApoE4). Possession of an ε4 allele is so strongly correlated with AD that it has been called the ‘susceptibility gene’.27 Heterozygotes for ApoE4 have a fivefold increased risk of developing AD, while homozygotes are estimated to have a staggering lifetime risk between 50% and 90%.54 Despite this threatening genetic heritage, the ApoE4 allele is neither required nor sufficient for development of AD: 50% of people with AD are not E4 carriers, and many E4 homozygotes never develop the disease. Chronic hyperinsulinaemia/insulin resistance elevates risk independently of ApoE status, with a 43% increased risk for AD from hyperinsulinism alone, regardless of genotype. Among insulin-resistant individuals who were not diagnosed diabetics (normoglycaemic due to hyperinsulinaemia), the risk for AD was double that of those without IR.15 As hyperinsulinaemia occurs in approximately 40% of people over age 60, it is not surprising to find a correlation between IR and a condition that preferentially strikes the aging.55
Although there are strong correlations between the ApoE4 genotype and AD, the majority of AD patients are not ApoE4 carriers. One potential aggravating factor for the ApoE4 genotype is that ApoE4 homozygotes produce 50% less hippocampal IDE compared to healthy controls, as well as AD patients who are not carriers of the ε4 allele.36 Thus, these individuals may have reduced capacity to degrade Aβ peptides relative to other genotypes, which would explain, in part, the severity of AD observed in ApoE4 carriers. However, it has not been determined whether the ApoE4 gene causes reduced IDE synthesis. The ApoE4 gene and reduced IDE expression could both presumably be the result of an overall hunter-gatherer genotype poorly suited for the modern diet’s evolutionarily discordant amount of refined carbohydrates.41,42,43,56
The single amino acid substitutions that differentiate the three ApoE isoforms affect tendency for apolipoproteins to become glycated, as well as determine binding affinity to any number of enzymes and receptors, which is why the isoforms are associated with different trends in serum low-density lipoprotein (LDL), very low–density lipoprotein (VLDL) and triglyceride measurements, with ApoE4 being associated with hypertriglyceridaemia and elevated LDL – common findings in metabolic syndrome and insulin resistance.56,57,58 Pre-agriculturalists presumably would have derived more of their calories from fat, protein and high-fibre, lower-starch, vegetable-based carbohydrates as opposed to grains and acellular carbohydrates, and may therefore have had a lower requirement for both insulin and IDE.41,43,59,60
The focus should be more on insulin, and less on cholesterol.