Research Fraud Bombshell Threatens Amyloid Hypothesis

by Jessica Hall

Alzheimer’s disease is a form of progressive dementia that we’ve labored to figure out for decades. Scientists made some headway with the amyloid hypothesis of Alzheimer’s disease, but progress is slow, and the hypothesis is incomplete. Now, a startling report has surfaced, accusing a prestigious Alzheimer’s researcher of systemic, deliberate research fraud. The results of this investigation could imperil the amyloid hypothesis as a whole.

The amyloid hypothesis of Alzheimer’s disease names a sticky protein called amyloid-beta as the disease’s primary cause. Scientists have identified “plaques and tangles” of amyloid-beta (Aβ) and tau (T) proteins in the brains of people who died of Alzheimer’s disease. But the amyloid hypothesis of the disease doesn’t fully explain its symptoms. Nor does it explain the scattershot absence of the protein in some Alzheimer’s victims’ brains.

But in 2006, Sylvain Lesné, of the University of Minnesota (UMN), shook up the Alzheimer’s research community with an extraordinary claim. Lesné and his team reported that they had discovered a “56-kDa soluble amyloid-β assembly,” a type of amyloid molecule which caused memory disruptions when they injected it into the brains of rats. (The “56-kDa” means 56 kiloDaltons, and it refers to the protein’s molecular weight.)

In the report, the authors propose that “Aβ*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer’s disease.”

‘Aβ Star is Born’

It looked like a smoking gun. The 2006 paper made it to Nature, one of the big-name scientific publishing houses. Alzforum, a “widely read online hub” for researchers, titled its writeup “Aβ Star is Born?” So, researchers leapt to explore the possibility of a treatment for Alzheimer’s that suppressed our Aβ precursor genes, or scrubbed Aβ itself from the brain.

Since then, much work has focused on amyloid plaques. More than two thousand papers cite Lesne’s 2006 paper. But it’s slow going. Since the amyloid explanation took precedence, it’s become difficult to get funding for research into other treatments or causes for the disease. Scientists complain that they’ve been…