Neurodegeneration in Normal Brain Aging and Disease
Abstract
Normal "healthy" aging is defined as aging without disease. Many aged people do not exhibit symptoms of disease and lead normal lives, but nonetheless display pathological changes that are characteristic of Alzheimer's disease (AD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and/or cerebrovascular disease (CVD). These changes are restricted to distinct brain regions and might represent preclinical stages of these disorders. This Perspective discusses arguments in favor of and against the hypothesis that pathological changes related to AD, PD, DLB, and CVD in the brains of nondemented elderly people represent early stages of these diseases rather than healthy aging. We conclude that early pathological disease-related changes do indeed constitute the beginning of AD, PD, DLB, and CVD rather than normal concomitants of aging, even in the absence of any clinical symptoms. Aging is, therefore, a major risk factor for these diseases but does not necessarily lead to age-related diseases.
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AβPs and NFTs are present well over a decade before death.
“The interval between initial ADD clinical diagnosis and death is approximately 8 years (129), but AβPs and NFTs are present well over a decade before death (130-138).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [133]
The aberrant accumulation of aggregated β-amyloid peptides (Aβ) as plaques is a hallmark of Alzheimer's disease (AD) neuropathology.
“The aberrant accumulation of aggregated β-amyloid peptides (Aβ) as plaques is a hallmark of Alzheimer’s disease (AD) neuropathology”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [193]
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- Authors
- Thal, D. R., Del Tredici, K., & Braak, H.
- Affiliations
- Goethe University Frankfurt (DE)
- Dietmar R. Thal is in the Department of Neuropathology at the University of Bonn Medical Center, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. Kelly Del Tredici and Heiko Braak are at the Institute for Clinical Neuroanatomy at Johann Wolfgang Goethe University, D-60590 Frankfurt am Main, Germany.(D.R.T.)
- Venue
- Science of Aging Knowledge Environment
- Published
- 2004-06-09
- Volume
- 2004
- Issue
- 23
- Pages
- pe26-pe26
- ISSN
- 1539-6150 (ISSN-L)
- OpenAlex
- W2116204362
- Cited by
- 149
- References
- 55
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 10 · 2014: 4 · 2013: 7 · 2012: 9
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science of Aging Knowledge Environment (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neurodegeneration, healthy brain aging, preclinical disease, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, cerebrovascular disease, aging as risk factor
- MeSH terms
- Aged, Aging, Alzheimer Disease, Brain, Cerebrovascular Disorders, Humans, Parkinson Disease, Neurodegenerative Diseases, Lewy Body Disease
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