DEC 30, 2019 6:55 PM PST

Amyloid Plaques May Not Come First in Alzheimer's

WRITTEN BY: Annie Lennon

It’s commonly thought that excessive build-up of amyloid plaques, destroying the connections between nerve cells, is the first sign of Alzheimer’s disease. Now however, a new study challenges this theory. 

For the study, researchers examined 747 participants without dementia from the Alzheimer’s Disease Neuroimaging Initiative. With each participant having received amyloid PET scan and structural MRIs, 305 were classified as cognitively normal, 289 had mild cognitive impairment (MCI), and 153 had objectively defined, subtle cognitive difficulties (Obj-SCD). Their mean age at the beginning of data collection was 72, and approximately half were men. 

After adjusting for age, education, sex, APOE ε4 allele frequency and baseline amyloid levels, the researchers found that tha Obj-SCD group had acceleated amyloid accumulation over 4 years than those in the cognitively normal group. They also had faster entorhinal cortical thinning, something known to negatively affect perceptual and cognitive function, than those in the cognitively normal group. 

By comparison, those with MCI did not display faster accumulation of amyloid plaques than cognitively normal participants. However, like those in the Obj-SCD group, they also faced accelerated entorhinal cortical thinning. They also displayed faster hippocampal atrophy, known to increase memory loss, over the study period. 

Lead author of the study, Kelsey Thomas, said, “Our research was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer's disease process.”

She added, “Much of the research exploring possible treatments for Alzheimer's disease has focused on targeting amyloid...But based on our findings, perhaps that focus needs to shift to other possible targets."

Despite these findings however, the researchers warn that their results do not necessarily refute the amyloid-first hypothesis. This comes as although baseline amyloid levels were numerically higher in the group with cognitive difficulties, they were not statistically higher, meaning that the start of fibrillar or soluble forms of beta-amyloid may have come before, if not coincided with, cognitive decline. Moreover, it remains unknown as to whether such cognitive issues are representative of longer-term, trait-like issues, or just more recent impairment. 

 

Sources: Medpage Today, Neurology and News Medical   

 

About the Author
  • Annie graduated from University College London and began traveling the world. She is currently a writer with keen interests in genetics, psychology and neuroscience; her current focus on the interplay between these fields to understand how to create meaningful interactions and environments.
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