Old Individuals with High Cognitive Function Exhibit Lower Accumulation of Amyloid-β and Tau

Neurodegenerative conditions are largely marked by the accumulation of a few different types of toxic protein aggregate, both amyloid-β and tau in the case of Alzheimer's disease. These few types of protein are capable of alteration in ways that seed other molecules of the same protein to also alter in the same way, linking to form solid deposits in and around cells. These deposits are clearly toxic - but, equally, it is becoming clear that removing amyloid-β doesn't appear to do much good in Alzheimer's patients, for reasons that continue to be debated. Perhaps because amyloid-β aggregation is an early phase of the condition, and the real damage is done by later mechanisms triggered by amyloid, such as tau aggregation. Perhaps because amyloid-β aggregation is a side-effect of more important mechanisms such as chronic viral infection and consequent neuroinflammation.

Super-agers, or individuals whose cognitive skills are above the norm even at an advanced age, have been found to have increased resistance to tau and amyloid proteins, according to new research. An analysis of positron emission tomography (PET) scans has shown that compared to normal-agers and those with mild cognitive impairment, super-agers have a lower burden of tau and amyloid pathology associated with neurodegeneration, which probably allows them to maintain their cognitive performance.

Data from the Alzheimer's Disease Neuroimaging Initiative was utilized to create three age- and education-matched groups of 25 super-agers, 25 normal-agers and 25 patients with mild cognitive impairment, all above 80 years old. In addition, 18 younger, cognitively normal, amyloid-negative controls were included in the comparison as a reference group. PET images obtained for all individuals and researchers compared the tau and amyloid burden between the four groups. A logistic regression was performed to identify genetic and pathophysiological factors best predicting aging processes.

No significant differences between super-agers and the younger control group were observed in terms of in vivo tau and amyloid burden. The normal-ager group exhibited tau burden in inferior temporal and precuneal areas and no significant differences in amyloid burden, when compared to the younger control group. Patients with mild cognitive impairment showed both high amyloid and high tau pathology burden. Differences in amyloid burden dissociated the normal-agers from those with mild cognitive impairment, whereas lower tau burden and lower polygenic risk predicted super-agers from mild cognitive impairment patients.

Link: https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=34196