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Vascular Pathology in Alzheimer Disease: Correlation of Cerebral Amyloid Angiopathy and Arteriosclerosis/Lipohyalinosis with Cognitive Decline
Abstract
Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the development of cognitive deficits in AD. A combination of both CAA and AS/LH may, therefore, contribute to neurodegeneration in AD. These data also suggest that small vessel disease due to arteriosclerosis and fibrolipohyalinosis is a potential target for the treatment of AD.
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“Both CAA and CCA variants of VAβ pathology have been described in AD autopsies and their relative preponderance has been linked to various APOE genotypes [40–43].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [41]
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Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431
Phases of Aβ-deposition in the human brain and its relevance for the development of AD
Thal, D. R., Rüb, U., Orantes, M., & Braak, H. (2002) · Neurology · doi:10.1212/wnl.58.12.1791 · Cited by 3,490
Self-citationProfound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796
Uber eine eigenartige Erkrankung der Hirnrinde
Alzheimer, A. (1907) · Medical Entomology and Zoology · Cited by 1,503
Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., & Van Hoesen, G. W. (1991) · Cerebral Cortex · doi:10.1093/cercor/1.1.103 · Cited by 1,380
Apolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070
A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study
Brun, A., & Englund, E. (1986) · Annals of Neurology · doi:10.1002/ana.410190306 · Cited by 1,014
Consensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease
(1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00057-2 · Cited by 981
Research works printed but not linked: 4
- Esiri MM Hyman BT Beyreuther K . Ageing and dementia. In: Lantos PL , ed. Greenfields neuropathology, 6th Edition. London: Arnold, 1997:153–233
- Kim, 1988, Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide, Neurosci Res Commun, 2, 121
- Kalimo H Kaste M Haltia M . Vascular diseases. In: Lantos PL . Greenfield's neuropathology, 6th Edition. London: Arnold, 1997:315–96
- Roman, 1993, Vascular dementia: Diagnostic criteria for research studies, Report of the NINDS-AIREN International Workshop. Neurology, 43, 250
Cited by
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Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050
Self-citationHachinski, V., Iadecola, C., Petersen, R. C., Breteler, M. M., Nyenhuis, D. L., Black, S. E., Powers, W. J., DeCarli, C., Merino, J. G., Kalaria, R. N., et al. (2006) · Stroke · doi:10.1161/01.str.0000237236.88823.47 · Cited by 1,722
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031
Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947
Patton, N., Aslam, T. M., MacGillivray, T., Pattie, A., Deary, I. J., & Dhillon, B. (2005) · Journal of Anatomy · doi:10.1111/j.1469-7580.2005.00395.x · Cited by 831
Metadata
- Authors
- Thal, D. R., Ghebremedhin, E., Orantes, M., & Wiestler, O. D.
- Affiliations
- University of Bonn (DE)
- Goethe University Frankfurt (DE)
- Corresponding author
- Thal, Dietmar Rudolf
- ORCID
- Thal, Dietmar Rudolf
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-12
- Volume
- 62
- Issue
- 12
- Pages
- 1287-1301
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1603244154
- Cited by
- 384
- References
- 51
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 14 · 2023: 14 · 2022: 29 · 2021: 23 · 2020: 26 · 2019: 22 · 2018: 15 · 2017: 10 · 2016: 15 · 2015: 22 · 2014: 23 · 2013: 21 · 2012: 11
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (TH624 4–1)
- 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
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- Alzheimer's disease, cerebral amyloid angiopathy, arteriosclerosis, lipohyalinosis, cerebral small vessel disease, cognitive decline, amyloid-beta deposition, neurofibrillary tangles, disease staging, vascular pathology, dementia, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Intracranial Arteriosclerosis, Cognition Disorders, Female, Humans, Male, Middle Aged, Cerebral Amyloid Angiopathy
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