Title:Neuropathological Correlates of Cerebral Multimorbidity
VOLUME: 10 ISSUE: 6
Author(s):Johannes Attems and Kurt Jellinger
Affiliation:Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, NE4 5PL Newcastle upon Tyne, UK.
Keywords:Alzheimer's disease, lewy body diseases, amyloid-β, α-synuclein, hyperphosphorylated tau, TDP-43.
Abstract:Age associated neurodegenerative diseases are characterized by intra- and extracellular aggregation and deposition
of misfolded proteins. The neuropathological classification of neurodegenerative diseases is based on the semiquantitative
assessment of these misfolded proteins, that constitute the neuropathological hallmark lesion for the respective
disease: e.g. Alzheimer's disease (AD), amyloid-β (Aβ) hyperphosphorylated tau (tau); Lewy body diseases, α-
synuclein (α-syn); frontotemporal lobar degeneration, tau, TDP-43, ubiquitin or FUS. In addition, cerebovascular lesions
are assessed for the diagnosis of vascular dementia. However, in brains of elderly patients suffering from neurodegenerative
diseases multiple pathologies are usually present and even in clinically characterized prospective cohorts additional
pathologies are frequently found at post mortem examination. On the other hand, various amounts of AD pathology are
frequently seen in brains of non-demented elderly and the threshold to cause clinical overt dementia is ill defined as additional
co-morbidities (e.g., cerebrovascular lesions) might lower the threshold for clinical dementia in some cases. It becomes
increasingly clear that the clinical picture of dementia in most aged patients results from a multimorbid condition in
the CNS rather than from one single disease and data from animal studies suggest that Aβ, tau, and α-syn interact in vivo
to promote the aggregation and accumulation of each other. We suggest that clinico-pathologocal correlative studies using
a more quantitative approach in the assessment of neuropathological lesions are warranted to elucidate cerebral multimorbidity
and to identify suitable targets for targeted therapeutic strategies against age associated neurodegeneration.
