Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship

By Peter T. Nelson, H. Braak, W. Markesbery. Journal of Neuropathology and Experimental Neurology, 2009

615 citations recorded by the source corpus.

Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensiveclinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but thepredictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.

Subfields: Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/03e9b05f056b246c611a18c7aa0375a96026fd31

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Citations in the corpus

Alzheimer’s disease: experimental models and reality (2017, background): “There have been many clinicopathological studies that have correlated amyloid plaques with cognitive deficits in AD, with an emerging picture that the strongest correlation exists in the earliest stages of the disease and this association greatly weakens as NFTs and neocortical degeneration become m”
Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models (2014, background): “First, the strongest correlation between amyloid plaques and cognition is in the early stages of the disease and this association weakens as NFTs and gross neocortical neurodegeneration become more widespread (Thal et al., 2002; Nelson et al., 2009b, 2012).”
Impact of multiple pathologies on the threshold for clinically overt dementia (2017, background): “Some propose the importance of AD pathology burden, and suggest neocortical Lewy body pathology is not sufficient to cause severe global cognitive impairment and that AD pathology must be present, reflecting a synergistic relationship [92].”
Classification and basic pathology of Alzheimer disease (2009, background): “Moreover, the relationship between the current intellectual scales and the pathology is not linear and is difficult to model [246].”
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012, background): “(142).”
Prion-like transmission of protein aggregates in neurodegenerative diseases (2010, background): “Neurofibrillary tangles and amyloid plaques are the classical neuropathological hallmarks of Alzheimer's diseas”