Association between apolipoprotein E e4 allele and arteriosclerosis, cerebral amyloid angiopathy, and cerebral white matter damage in Alzheimer’s disease
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OBJECTIVE: To investigate the association between white matter damage, as evidenced by myelin loss (ML), the extent of cerebral amyloid angiopathy (CAA), or arteriosclerosis (Art), and apolipoprotein E (ApoE) e4 allele in Alzheimer's disease (AD), in order to understand the causes of damage to white matter in AD and its contribution to the pathogenesis of the disorder. MATERIALS AND METHODS: Brain tissues were obtained from 94 patients with AD confirmed by autopsy. ApoE genotyping was performed by PCR on DNA extracted from frontal cortex or cerebellum. CAA and Art were assessed on Weigert's haematoxylin and eosin stained sections in frontal, temporal, parietal, and occipital cortices; the extent of ML was scored on Luxol fast blue stained sections of these regions. RESULTS: The ApoE e4 allele frequency in the 61 patients with ML was not significantly different from that in the 33 patients without ML, nor did this differ in the 84 patients with Art from that in the 10 patients without Art. There were no significant differences in the proportions of patients with genotypes containing 0, 1, or 2 ApoE e4 alleles in the presence or absence of ML or Art. The mean ML, Art, or CAA scores within each region, and the total scores summed across all four brain regions, did not differ between patients with 0, 1, or 2 ApoE e4 alleles. However, the mean ML severity score in the occipital cortex was significantly greater than that in the frontal or temporal cortices in patients with 1 or 2 ApoE e4 alleles. The severity of CAA in the occipital cortex was significantly higher than that in other areas of cortex in patients with 0 or 2 ApoE e4 alleles. The mean Art score in the occipital cortex was greater than that in the temporal cortex in patients with two ApoE e4 alleles and was higher than that in the frontal cortex in patients with one ApoE e4 allele. CONCLUSIONS: The likelihood of patients with AD suffering from CAA, Art, or ML is not influenced by ApoE e4 allele, nor is the overall burden of these pathological changes in the brain. However, the distribution of ML, CAA, and Art within the brain is at least partly influenced by genotype and dosage of ApoE e4 allele, with the occipital cortex being more severely affected by all of these pathological changes in e4 allele bearers, particularly when two ApoE e4 alleles are present.
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Rosiglitazone was tested for secondary prevention of cognitive decline in mild AD among persons without T2D and was found to be non-efficacious in a phase III trial after promising results in a pilot study.
“The thiazolidinedione rosiglitazone was tested for secondary prevention of cognitive decline in mild AD among persons without T2D and was found to be non-efficacious in a phase III trial[71] after promising results in a pilot study [72].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [71]
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- Authors
- Tian, J.
- Affiliations
- Beijing University of Chinese Medicine (CN)
- Corresponding author
- Tian, J
- ORCID
- Tian, J
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2004-05-01
- Volume
- 75
- Issue
- 5
- Pages
- 696-699
- ISSN
- 0022-3050 (ISSN-L)
- PMC
- PMC1763560
- OpenAlex
- W2125471430
- Cited by
- 39
- References
- 40
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- 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, cerebral amyloid angiopathy, arteriosclerosis, white matter injury, demyelination, APOE genotype, occipital cortex, genetic risk factors, neuropathology, autopsy brain tissue, Luxol fast blue staining, frontal cortex, temporal cortex
- MeSH terms
- Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Cerebellum, Intracranial Arteriosclerosis, Female, Frontal Lobe, Genotype, Humans, Male, Myelin Sheath, Occipital Lobe, Temporal Lobe, Prevalence, Polymerase Chain Reaction, Cerebral Amyloid Angiopathy, Apolipoprotein E4
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