Cited by 168Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Neuropathological Diagnosis of Alzheimer’s Disease: A Perspective from Longitudinal Clinicopathological Studies

Dickson, D.W·1997·Neurobiology of Aging

DOI 10.1016/s0197-4580(97)00065-1

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Abstract

Alzheimer's disease (AD) is the most common cause of primary progressive dementia. It is defined by its pathological features, because the clinical syndrome of dementia lacks specificity. Although the brain in AD has many structural alterations, the two cardinal pathological features and sine qua non of AD are senile plaques and neurofibrillary degeneration. The latter takes the form of neurofibrillary tangles composed of paired helical filaments, as well as degenerating neurites within the neuropil ("neuropil threads") and within a diagnostically significant subset of SP, referred to as "neuritic plaques." All SP contain amyloid, but not all have pair helical filament-type neurites. The presence of even a small number of plaques with paired helical filament-type neurites in the neocortex is associated with cognitive impairment, and this lesion may be the most specific histopathological feature of AD. Although these observations suggest that the major difference between SP in aging and AD relate to differences in neuritic degeneration, more recent studies have also indicated that amyloid deposits are biochemically heterogenous and that amyloid deposits in aging may be different from those in AD. As more specific markers become available for recognizing AD-specific structural lesions, refined neuropathological diagnostic criteria will evolve. In the meantime, a practical neuropathological approach to the diagnosis of AD requires both widespread neocortical SP and an advanced stage of neurofibrillary degeneration. Using these criteria, it is very unlikely that AD will be diagnosed in an individual who was not demented in life. The rationale for adopting this conservative approach is that our knowledge is incomplete with respect to fundamental differences between the lesions in aging and AD.

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Authors: Dickson, D. W.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Dickson, D.W
ORCID: Dickson, D.W
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 1997-07
Volume: 18
Issue: 4
Pages: S21-S26
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/s0197-4580(97)00065-1
OpenAlex: W2011769584
Cited by: 168
References: 44
Citations by year: 2026: 4 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 11 · 2018: 15 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 12
FWCI: 1.02
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p01ag006803-11)
U.S. Public Health Service (NIA 03949)
National Institute on Aging (AG-06803)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, neuropathological diagnosis, amyloid plaques, neurofibrillary degeneration, paired helical filaments, neuritic plaques, amyloid deposits, neuropil threads, dementia, clinicopathological correlation, diagnostic criteria
MeSH terms: Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Cell Count, Diagnosis, Differential, Humans, Longitudinal Studies, Middle Aged, Parkinson Disease, Prospective Studies, Severity of Illness Index, Neurofibrillary Tangles, Neuropil Threads, Plaque, Amyloid

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Neuropathological Diagnosis of Alzheimer’s Disease: A Perspective from Longitudinal Clinicopathological Studies

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