A company has started selling the first blood test to help diagnose Alzheimer’s disease, a leap for the field that could make it much easier for people to learn whether they have dementia. It also raises concern about the accuracy and impact of such life-altering news.
Independent experts are leery because key test results have not been published and the test has not been approved by the U.S. Food and Drug Administration — it’s being sold under more general rules for commercial labs.
The test is not intended for general screening or for people without symptoms — it’s aimed at people 60 and older who are having thinking problems and are being evaluated for Alzheimer’s … It measures two types of amyloid particles plus various forms of a protein that reveal whether someone has a gene that raises risk for the disease. These factors are combined in a formula that includes age, and patients are given a score suggesting low, medium or high likelihood of having amyloid buildup in the brain.
The State of the Science:
a) In favor of the approach, co-authored by one of the developers of the test: Amyloid‑B and Tau at the Crossroads of Alzheimer’s Disease (Advances in Experimental Medicine and Biology).
- Abstract: Alzheimer’s disease (AD) is the most common form of dementia characterized neuropathologically by senile plaques and neurofibrillary tangles (NFTs). Early breakthroughs in AD research led to the discovery of amyloid‑B as the major component of senile plaques and tau protein as the major component of NFTs. Shortly following the identification of the amyloid‑B (AB) peptide was the discovery that a genetic mutation in the amyloid precursor protein (APP), a type1 transmembrane protein, can be a cause of autosomal dominant familial AD (fAD). These discoveries, coupled with other breakthroughs in cell biology and human genetics, have led to a theory known as the “amyloid hypothesis”, which postulates that amyloid‑B is the predominant driving factor in AD development. Nonetheless, more recent advances in imaging analysis, biomarkers and mouse models are now redefining this original hypothesis, as it is likely amyloid‑B, tau and other pathophysiological mechanism such as inflammation, come together at a crossroads that ultimately leads to the development of AD.
b) Challenging the basic approach: The case for rejecting the amyloid cascade hypothesis (Nature Neuroscience).
- Abstract: Alzheimer’s disease (AD) is a biologically complex neurodegenerative dementia. Nearly 20 years ago, with the combination of observations from biochemistry, neuropathology and genetics, a compelling hypothesis known as the amyloid cascade hypothesis was formulated. The core of this hypothesis is that it is pathological accumulations of amyloid‑B, a peptide fragment of a membrane protein called amyloid precursor protein, that act as the root cause of AD and initiate its pathogenesis. Yet, with the passage of time, growing amounts of data have accumulated that are inconsistent with the basically linear structure of this hypothesis. And while there is fear in the field over the consequences of rejecting it outright, clinging to an inaccurate disease model is the option we should fear most. This Perspective explores the proposition that we are over-reliant on amyloid to define and diagnose AD and that the time has come to face our fears and reject the amyloid cascade hypothesis.
The News in Context:
- Brain scans show lower accumulation of tau and amyloid pathology among cognitive “super-agers”
- Study challenges the “seductive” amyloid hypothesis of Alzheimer’s disease (AD)
- Cognitive training, diet, exercise, and vascular management seen to improve cognition even in people with genetic predisposition for dementia (APOE e4)
- Report: 35% of worldwide dementia cases could be prevented by modifying these 9 modifiable risk factors
- Build Your Cognitive Reserve: Interview with Yaakov Stern