Help us: Donate
Follow us on:
Γ—

Menu

Back

Challenging the Alzheimer’s Amyloid Hypothesis

Journal Club July 2021

Journal ClubJournal Club

Journal Club returns on July 27th at noon Eastern / 17:00 UK live on our Facebook page.

A new way to look at Alzheimer’s

The topic for this month will be a new study that challenges the amyloid hypothesis of Alzheimer’s disease with new human data. The data suggests that the cognitive impairment that accompanies Alzheimer’s may hinge not on amyloid accumulation but upon the presence, or lack thereof, of the soluble amyloid-beta peptide.

Join Dr. Oliver Medvedik and guests as we take a look at the data and discuss the findings. If you are a Lifespan Hero, you can even join us live on the call; details will go to the email you registered as a Hero with, and you can also check the Heroes corner.

Abstract

Brain amyloidosis does not invariably predict dementia. We hypothesized that high soluble 42-amino acid Ξ² amyloid (AΞ²42) peptide levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis. This cross-sectional study of 598 amyloid-positive participants in the Alzheimer’s Disease Neuroimaging Initiative cohort examined whether levels of soluble AΞ²42 are higher in amyloid-positive normal cognition (NC) individuals compared to mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and whether this relationship applies to neuropsychological assessments and hippocampal volume measured within the same year. All subjects were evaluated between June 2010 and February 2019. Brain amyloid positivity was defined as positron emission tomography-based standard uptake value ratio (SUVR) β‰₯1.08 for [18] F-florbetaben or 1.11 for [18]F-florbetapir, with higher SUVR indicating more brain amyloidosis. Analyses were adjusted for age, sex, education, APOE4, p-tau, t-tau, and centiloids levels. Higher soluble AΞ²42 levels were observed in NC (864.00 pg/ml) than in MCI (768.60 pg/ml) or AD (617.46 pg/ml), with the relationship between NC, MCI, and AD maintained across all amyloid tertiles. In adjusted analysis, there was a larger absolute effect size of soluble AΞ²42 than SUVR for NC (0.82 vs. 0.40) and MCI (0.60 vs. 0.26) versus AD. Each standard deviation increase in AΞ²42 was associated with greater odds of NC than AD (adjusted odds ratio, 6.26; p < 0.001) or MCI (1.42; p = 0.006). Higher soluble AΞ²42 levels were also associated with better neuropsychological function and larger hippocampal volume.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

A Synthetic Gene Oscillator to Slow Cellular Aging

The Journal Club returns on Tuesday May 23rd at 12:00 Eastern with your host, Dr. Oliver Medvedik. This month we...

Reducing DNA Damage With DREAM

In the Journal Club this month we will exploring a new study published in Nature Structural and Molecular Biology, where...

Human Fasting Modulates Macrophage Function

The Journal Club returns on Tuesday 28th March at 12:00 PM Eastern time to the Lifespan.io Facebook channel. This month...

mRNA-Encapsulating Extracellular Vesicles for Collagen

The Journal Club, hosted by Dr. Oliver Medvedik, returns to the Lifespan.io Facebook page at 12:00 on Tuesday, February 28th....

Literature

[1] Sturchio, A., Dwivedi, A. K., Young, C. B., Malm, T., Marsili, L., Sharma, J. S., … & Espay, A. J. (2021). High cerebrospinal amyloid-Ξ² 42 is associated with normal cognition in individuals with brain amyloidosis. EClinicalMedicine, 100988.

No Comments
Write a comment:

*

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.