It's important to note that while "RES treatment altered Aβ40 levels in CSF and plasma," "RES had no effect on Aβ42 in CSF or plasma, CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which were prespecified primary outcomes of the trial." In nearly all studies, CSF Aβ40 levels remain stable thru'out the leadup into and course of AD, so altering that more or less stable trajectory most likely has no prognostic or causal significance. By contrast, CSF Aβ42 levels quite consistently fall during the preclinical phase, continue to fall or remain stable during the transition from MCI to AD, and then remain stable after dementia onset. So the fact that there's no effect on Aβ42 — or on CSF tau or phospho-tau-181, hippocampal volume, or entorhinal cortex thickness, all of which are known predictors of AD dementia and were prespecified primary outcomes of the trial — is inconsistent with a protective effect of RES on AD risk or onset.
The fact that RES use "was associated with a loss of brain volume and an increase in ventricular [non-parenchymal, CSF-filled "empty" brain space] volume" might conceivably be "explained by reduced edema and inflammation" in the brain — there's reason to think this is what's happening with similar paradoxical findings in Abeta immunotherapy — but of course it could also be the result of increased brain atrophy.
Beta Amyloids note that Aβ40 is an important marker to predisposition of A/D
http://en.wikipedia....ki/Amyloid_beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients
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A number of genetic, cell biology, biochemical and animal studies support the concept that Aβ plays a central role in the development of Alzheimer’s disease pathology.....
Brain Aβ is elevated in patients with sporadic Alzheimer’s disease. Aβ is the main constituent of brain parenchymal and vascular amyloid; it contributes to cerebrovascular lesions and is neurotoxic.[23][24][25][26] It is unresolved how Aβ accumulates in the central nervous system and subsequently initiates the disease of cells. Some researchers have found that the Aβ oligomers induce some of the symptoms of Alzheimer's Disease by competing with insulin for binding sites on the insulin receptor, thus impairing glucose metabolism in the brain.[27] Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes alpha- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein).[28][29][30][31] Aβ circulates in plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) mainly as soluble Aβ40[23][32] Senile plaques contain both Aβ40 and Aβ42,[33] while vascular amyloid is predominantly the shorter Aβ40. Several sequences of Aβ were found in both lesions.[34][35][36] Generation of Aβ in the CNS may take place in the neuronal axonal membranes after APP-mediated axonal transport of β-secretase and presenilin-1.[37]
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Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in neuritic plaques)[38] have been implicated in the pathogenesis of both familial and sporadic Alzheimer's disease.
Formation
Aβ is formed after sequential cleavage of the amyloid precursor protein (APP), a transmembrane glycoprotein of undetermined function. APP can be cleaved by the proteolytic enzymes α-, β- and γ-secretase; Aβ protein is generated by successive action of the β and γ secretases. The γ secretase, which produces the C-terminal end of the Aβ peptide, cleaves within the transmembrane region of APP and can generate a number of isoforms of 36-43 amino acid residues in length. The most common isoforms are Aβ40 and Aβ42; the longer form is typically produced by cleavage that occurs in the endoplasmic reticulum, while the shorter form is produced by cleavage in the trans-Golgi network.[41] The Aβ40 form is the more common of the two, but Aβ42 is the more fibrillogenic and is thus associated with disease states. Mutations in APP associated with early-onset Alzheimer's have been noted to increase the relative production of Aβ42, and thus one suggested avenue of Alzheimer's therapy involves modulating the activity of β and γ secretases to produce mainly Aβ40.[42] Aβ is destroyed by several amyloid-degrading enzymes including neprilysin.[43]
(Thus the Resveratrol had a positive effect compared to the Placebo Group in lowering their chances of acquiring Alzheimers)