A 2018 article in Nature (https://www.nature.com/articles/d41586-018-05719-4) explored the long-held assumption that the amyloid-β protein clumps together and forms deposits in the brain, damaging neurons and synapses and causing Alzheimer’s disease (AD). This is referred to as the Amyloid Theory or Amyloid Cascade Hypothesis. If you can attack the amyloid plaques, the theory states, then you can treat Alzheimer's disease. There is another assumption that tau proteins, which are neurofibrillary tangles, are also responsible for AD...hence the"Plaques and Tangles" label.
The amyloid theory has not been accepted by all researchers in the field, since so many of the drugs developed to focus on reducing or eliminating amyloid plaques have proven to be largely ineffective at improving memory and cognition. In fact, many people have amyloid plaques with no signs of cognitive impairment. We saw this earlier in the famous Nun Study, where over 600 nuns participated in brain research. Of those who donated their brains for study, many had accumulations of amyloid (and tau tangles) with no signs of dementia. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734290/)
Of course, now we are seeing literature calling out a lack of - or decrease in - amyloid leading to cognitive impairment (https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220808). More to come on this as pharmaceutical research continues to look for more effective solutions/treatments.
The Journal of Alzheimer’s Disease published an article this month (Oct. 2022) addressing the amyloid hypothesis. Researchers found that high levels of amyloid-β42 are associated with normal brain functioning. One of the biggest challenges faced by dementia research in the past is that the plaques can only be seen post-mortem and via tissue biopsies; the latter being extremely invasive and not very popular. Newly developed imaging technologies, lumbar punctures, and newly developed blood tests show promise. University of California, San Francisco states:
Amyloid PET imaging represents a potential major advance in the assessment of those with cognitive impairment. The scan visualizes plaques present in the brain, which are prime suspects in damaging and killing nerve cells in Alzheimer's. Before amyloid PET, these plaques could only be detected by examining the brain at autopsy. Amyloid PET scanning makes amyloid plaques "light up" on a brain PET scan, enabling, for the first time, accurate detection of plaques in living people.
However, the debate and studies continue. If amyloid accumulation is not the culprit of AD, is the reduction of plaques the key to better understanding AD pathology or other cognitive impairments? Stay tuned...
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