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Measurable Amyloid Buildup Occurs Significantly Before Alzheimer's Disease


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Posted 14 June 2017 - 10:37 AM


Named and formally recognized age-related diseases are the late stages of processes of damage that start much earlier in life. So it is never a surprise to see that specific forms of damage strongly associated with any one specific age-related disease can be detected in smaller amounts earlier in old age, and that the people with more of that damage have a higher risk of later exhibiting the disease state. In the case of the research materials noted here, the disease is Alzheimer's, and the damage is accumulation of amyloid-β, a form of misfolded protein that accumulates in the brain. It and its surrounding halo of chemical interactions disrupt the correct function of brain cells, ultimately causing significant neurodegeneration.

The obvious solution here is to try to remove the amyloid, and in fact the Alzheimer's research community has and continues to spend considerable effort on this goal. It is one of the few areas where mainstream aging research aligns with the goals of the SENS rejuvenation research programs: identify the root cause damage that produces differences between old and young tissue, and repair it. Sadly, safe and effective clearance of amyloid has proven to be far more challenging than hoped. The field is littered with failed attempts, largely forms of immunotherapy, and only in the past couple of years have there been signs of success in human trials. Nonetheless, removing amyloid, and then expanding efforts to other forms of repair therapy, is the only game in town if the goal is to cure age-related neurodegenerative disease rather than just slow it down it little.

Older adults with elevated levels of brain-clogging plaques - but otherwise normal cognition - experience faster mental decline suggestive of Alzheimer's disease, according to a new study that looked at 10 years of data. Just about all researchers see amyloid plaques as a risk factor for Alzheimer's. However, this study presents the toxic, sticky protein as part of the disease - the earliest precursor before symptoms arise. Notably, the incubation period with elevated amyloid plaques - the asymptomatic stage - can last longer than the dementia stage. "To have the greatest impact on the disease, we need to intervene against amyloid, the basic molecular cause, as early as possible."

The researchers likened amyloid plaque in the brain to cholesterol in the blood. Both are warning signs with few outward manifestations until a catastrophic event occurs. Treating the symptoms can fend off the resulting malady - Alzheimer's or a heart attack - the effects of which may be irreversible and too late to treat. The researchers hope that removing amyloid at the preclinical stage will slow the onset of Alzheimer's or even stop it.

One in three people over 65 have elevated amyloid in the brain, and the study indicates that most people with elevated amyloid will progress to symptomatic Alzheimer's within 10 years. The study uses 10 years of data from the Alzheimer's Disease Neuroimaging Initiative, an exploration of the biomarkers that presage Alzheimer's. Although elevated amyloid is associated with subsequent cognitive decline, the study did not prove a causal relationship. Researchers measured amyloid levels in 445 cognitively normal people via cerebrospinal fluid taps or positron emission tomography (PET) scans: 242 had normal amyloid levels and 202 had elevated amyloid levels. Cognitive tests were performed on the participants, who had an average age of 74. Although the observation period lasted 10 years, each participant, on average, was observed for three years. The maximum follow-up was 10 years.

The elevated amyloid group was older and less educated. Additionally, a larger proportion of this group carried at least one copy of the ApoE4 gene, which increases the odds that someone will develop Alzheimer's. Based on global cognition scores, at the four-year mark, 32 percent of people with elevated amyloid had developed symptoms consistent with the early stage of Alzheimer's disease. In comparison, only 15 percent of participants with normal amyloid showed a substantial decline in cognition. Analyzing a smaller sample size at year 10, researchers noted that 88 percent of people with elevated amyloid were projected to show significant mental decline based on global cognitive tests. Comparatively, just 29 percent of people with normal amyloid showed cognitive decline.

Link: https://news.usc.edu...-of-alzheimers/


View the full article at FightAging




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