Before Aβ snaps into the rigid amyloid fibrils that predominate in plaques, the peptide clumps into soluble oligomers. Deemed the most toxic form of Aβ, these fledgling aggregates have also been devilishly difficult to detect. Now, researchers led by Valerie Daggett at the University of Washington in Seattle report that a soluble-oligomer binding assay—SOBA—picks them up in plasma, distinguishing controls and people with Alzheimer’s disease with 99 percent accuracy. The assay uses a designer peptide to capture oligomers that fold into α-sheets, a secondary structure that forms in the earliest stages of oligomerization. SOBA detected Aβ42 oligomers among controls who later developed mild cognitive impairment, suggesting it could identify people in the preclinical stage of AD. 

“The formation of toxic Amyloid β-peptide (Aβ) oligomers is one of the earliest events in the molecular pathology of Alzheimer’s Disease (AD). These oligomers lead to a variety of downstream effects, including impaired neuronal signaling, neuroinflammation, tau phosphorylation, and neurodegeneration, and it is estimated that these events begin 10 to 20 y before the presentation of symptoms. Toxic Aβ oligomers contain a nonstandard protein structure, termed α-sheet, and designed α–sheet peptides target this main-chain structure in toxic oligomers independent of sequence.”

“AltPep Corporation, a privately held biotechnology company developing early disease-modifying treatments and detection tools for amyloid diseases, today announced that this week the Proceedings of the National Academy of Sciences (PNAS) will publish results of a groundbreaking study demonstrating a customized, synthetic peptide’s ability to selectively detect Alzheimer’s disease.”

Today, by and large, patients receive a diagnosis of Alzheimer’s only after they exhibit well-known signs of the disease, such as memory loss. By that point, the best treatment options simply slow further progression of symptoms.

But research has shown that the seeds of Alzheimer’s are planted years — even decades — earlier, long before the cognitive impairments surface that make a diagnosis possible. Those seeds are amyloid beta proteins that misfold and clump together, forming small aggregates called oligomers. Over time, through a process scientists are still trying to understand, those “toxic” oligomers of amyloid beta are thought to develop into Alzheimer’s.

“Amyloid diseases are linked to protein misfolding whereby the amyloidogenic protein undergoes a conformational change, aggregates and eventually forms amyloid fibrils…”

Lecture at UW on Oct 13, 2022 with Valerie Daggett, AltPep CEO. Learn about her groundbreaking work in Alzheimer’s and other amyloid…

Alzheimer’s disease researchers were buoyed by positive data released Tuesday from a large clinical trial of an experimental therapy being developed by Biogen and Eisai.

The early data suggest that the treatment, called lecanemab, eases cognitive decline. The findings also rejuvenated hope in a therapeutic approach targeting peptides that form nasty clumps in the brain of people with Alzheimer’s.