Susan K. Rohde (Netherlands)
Amsterdam UMC
Human genetics, section Genomics of Neurodegeneration and Aging (100-plus Study)
In November 2020, Susan has started her PhD project at the 100-plus Study. She is investigating the neuropathological and functional characteristics of the centenarian brain. Susan is especially interested in a rare genetic mutation in the PLCG2 gene that is enriched in our cohort of cognitively healthy centenarians. This genetic mutation protects against multiple types of dementia and increases the likelihood to reach extreme ages. We hope to understand how this genetic mutation delays the onset of dementia and alters brain processes. This knowledge may identify promising therapeutic targets for AD.

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 Conference Calendar

NEUROPATHOLOGICAL HALLMARKS OF NEURODEGENERATIVE DISEASES DO NOT ASSOCIATE WITH COGNITIVE PERFORMANCE IN CENTENARIANS

Session Name
0780 - NEUROPATHOLOGY IN AD, LBD AND OTHER DEMENTIA 2 (ID 134)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:30 PM
Room
ONSITE: 133-134
Lecture Time
04:15 PM - 04:30 PM
Presenter

Abstract

Aims

Hallmarks of neurodegenerative diseases accumulate with age in the brains of non-demented individuals, which has implications for diagnosis and interpretation of the pathological role of these hallmarks in extreme aging. To investigate the separability of pathological hallmarks of Alzheimer’s disease (AD), we assessed AD-related pathology in an age-continuum of AD and non-demented subjects up to extreme aging. Furthermore, we determined to what extent neuropathology loads discriminate between cognitive performance in centenarians.

Methods

NIA-Reagan amyloid phases, Braak neurofibrillary tangle stages, and CERAD neuritic plaque scores were analyzed in an age continuum comprising 849 AD (aged 37-102), 653 non-demented (aged 16-99) and 86 centenarian (aged 100-115) donors. Centenarian brain tissue was additionally scored for the load of TAR DNA-binding protein 43, Lewy bodies and granulovacuolar degeneration and divided in demented (MMSE <=24, n=39) and non-demented (MMSE>24, n=47), based on MMSE assessment 8.8 (±6.97) months prior to donation.

Results

With increasing age-at-death, AD related neuropathology load increased in non-demented individuals, and decreased in AD cases, converging at around 100 years of age. In centenarians, neuritic plaque load associated with cognitive decline (p=0.02), but all other assessed neuropathologies did not associate with cognitive performance.

Conclusions

The ability of the classic AD-related neuropathological hallmarks to distinguish between health and disease decreases with age until at extreme ages. This suggests that: (1) with age, the ability to maintain cognitive health increasingly depends on being resilient against the toxic effects associated with these pathologies; and/or (2) that neuropathological hallmarks accumulated in older individuals may be a harmless consequence of aging.

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