Cited by 134Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Parenchymal and vascular Aβ‐deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease

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Thal, Dietmar Rudolf, Griffin, W. Sue T., Braak, Heiko·2008·Journal of Cellular and Molecular Medicine

Abstract

Introduction The deposition of Aβ Neurotoxicity of Aβ Contribution of CAA to the degeneration of neurons Clinical impact of Aβ and its therapeutic possibilities Conclusions The deposition of the amyloid β‐protein (Aβ) is one of the pathological hallmarks of Alzheimer's disease (AD). Aβ‐deposits show the morphology of senile plaques and cerebral amyloid angiopathy (CAA). Senile plaques and vascular Aβ‐deposits occur first in neocorti‐cal areas. Then, they expand hierarchically into further brain regions. The distribution of Aβ plaques throughout the entire brain, thereby correlates with the clinical status of the patients. Imaging techniques for Aβ make use of the hierarchical distribution of Aβ to distinguish AD patients from non‐AD patients. However, pathology seen in AD patients represents a late stage of a pathological process starting 10–30 years earlier in cognitively normal individuals. In addition to the fibrillar amyloid of senile plaques, oligomeric and monomeric Aβ is found in the brain. Recent studies revealed that oligomeric Aβ is presumably the most toxic Aβ‐aggregate, which interacts with glutamatergic synapses. In doing so, dendrites are presumed to be the primary target for Aβ‐toxicity. In addition, vascular Aβ‐deposits can lead to capillary occlusion and blood flow disturbances presumably contributing to the alteration of neurons in addition to the direct neurotoxic effects of Aβ. All these findings point to an important role of Aβ and its aggregates in the neurodegenerative process of AD. Since there is already significant neuron loss in AD patients, treatment strategies aimed at reducing the amyloid load will presumably not cure the symptoms of dementia but they may stop disease progression. Therefore, it seems to be necessary to protect the brain from Aβ‐toxicity already in stages of the disease with minor neuron loss before the onset of cognitive symptoms.

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Authors
Thal, D. R., Griffin, W. S. T., & Braak, H.
Affiliations
  • Universität Ulm (DE)
  • University of Arkansas Medical Center (US)
  • Goethe University Frankfurt (DE)
Corresponding author
Thal, Dietmar Rudolf
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2008-10
Volume
12
Issue
5b
Pages
1848-1862
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
OpenAlex
W1985063020
Cited by
134
References
167
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 9 · 2016: 14 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 9
FWCI
0.72
Type
journal article
Language
en
Open access
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc)
Funders
  • Chinese Academy of Agricultural Sciences
  • National Institute on Aging (AG 12411, P01AG012411)
Topics
  • Health Sciences › Medicine › Physiology › 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, amyloid-beta, amyloid plaques, cerebral amyloid angiopathy, vascular amyloid deposits, amyloid-beta oligomers, neurodegeneration, glutamatergic synapses, capillary occlusion, blood flow disturbance, cognitive impairment, amyloid imaging, disease progression
MeSH terms
Alzheimer Disease, Blood Vessels, Cognition, Dendrites, Humans, Models, Neurological, Neurons, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Plaque, Amyloid

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