The article here notes that researchers find cognitively healthy centenarians exhibit levels of protein aggregation and other brain lesions typical of people showing symptoms of neurodegenerative diseases. They are in some way more resistant, but why this is the case is a continuing research project. It is possible to identify specific gene variants and more youthful gene expression for some genes in cognitively healthy older individuals, but it is long trek from that data to an understanding of the mechanisms involved.
Researchers initially aimed to recruit 500 cognitively healthy centenarians. As of June 2021, 406 had signed up. Their average age when they joined was 101; the oldest is now 107. Seventy percent are women; 43 percent still live independently. About 30 percent have agreed to donate their brains after death and, to date, 95 of them have passed away. Researchers have presented the neuropathology findings from 85 of those.
At autopsy, some of these centenarians were found to have had pathologies typical of people with Alzheimer's disease (AD). Many had been in stage 2 or 3 amyloidosis when they died, as judged by NIA criteria, and had accumulated stage 2 or even stage 3 neuritic plaques per CERAD scores. All were in at least Braak stage I for neurofibrillary tangles, though the majority were at stage III or higher. The brains weighed about as much as those from people who had had AD dementia, but neither plaques nor tangles correlated with cognitive assessments.
The same was true for a host of other age-related pathologies, including cerebral amyloid angiopathy, TDP-43 proteinopathy, Lewy bodies, hippocampal sclerosis, granulovacuolar degeneration, atherosclerosis, and vascular infarcts. Many centenarians had at least one of these. Across all of these pathologies, increased levels in the postmortem brain generally came with lower cognitive scores before death, but the associations were weak. Of all neuropathological substrates tested, tangles correlated most robustly with lower performance, but these healthy centenarians seemed surprisingly resistant even to the effects of high levels of tangles.
Scientists compared the centenarians' proteomes to those from 50- to 95-year-old people with AD and to 50- to 90-year-old healthy controls. They found that, while concentrations of about two dozen proteins fall with age, in centenarians, these protein levels were higher than expected for their age. For four other proteins that normally tick up with age, levels remained steady in the centenarians. The proteins that bucked these trends included those involved in microtubule and intermediate filament biology, myelination, the immune system, basic metabolism, and protein transport. "In a nutshell, these centenarians have younger-looking brains."
Link: https://www.alzforum...u-immune-system
View the full article at FightAging
