Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down syndrome

Topic: Brain proteins, microglia and lab models

Study of the hippocampal formation of 82 subjects, including 25 control subjects from 33 to 83 years of age, 34 subjects with Alzheimer disease (AD) from 65 to 89 years of age, and 23 subjects with Down syndrome (DS) from 33 to 72 years of age, revealed hippocampal vasculopathy with fibrosis and calcification (VFC) in 40% of control, 59% of AD, and 4% of DS subjects. VFC starts in the precapillaries/capillaries in the molecular layer of the dentate gyrus (DG) and expands to the granule cell and polymorphic cell layer of the DG, and to the stratum lacunosum/molecular in the CA1 sector. Vasculopathy spreads from the tail to the body and, in a few cases, to the head of the hippocampal formation. Light and electron microscopy reveal thickening of the vascular wall with fibrosis, calcification, and enforcement of the astrocyte interface with vessels with anchorage densities associated with hemidesmosome-like structures. In moderately and severely affected cases, fragmentation and removal of calcified and occluded vessels result in local reduction of vascular network. In two AD subjects, severe vascular calcification extending from the tail to the head of the hippocampal formation was associated with loss of almost all neurons in the CA1 sector and in the subiculum proper, corresponding to hippocampal sclerosis. The topography of affected vessels and the patterns of neuronal loss reflect the middle hippocampal artery distribution with its precapillary/capillary network. The similar prevalence of vasculopathy in the AD group and in the age-matched control group, and the presence of hippocampal VFC in only one subject in the DS cohort, 96% of which is affected by Alzheimer-type pathology, oppose the link between AD and this form of vasculopathy. However, severe VFC affects the pattern of AD pathology locally by deletion of neurofibrillary degeneration and beta-amyloidosis in the CA1 sector, subiculum proper, and the molecular layer of the dentate gyrus. Hippocampal VFC appears to be a form of vascular pathology with a unique predilection for the middle hippocampal artery and corresponding capillary network, which results in patchy neuronal loss in moderately affected subjects and in almost total neuronal loss in the area of impaired blood supply in severely affected subjects. These observations suggest an etiologic link between hippocampal VFC and hippocampal sclerosis.

Key findings

• Study of the hippocampal formation of 82 subjects, including 25 control subjects from 33 to 83 years of age, 34 subjects with Alzheimer disease (AD) from 65 to 89 years of age, and 23 subjects with Down syndrome (DS) from 33 to 72 years of age, revealed hippocampal vasculopathy with fibrosis and calcification (VFC) in 40% of control, 59% of AD, and 4% of DS subjects.
• Light and electron microscopy reveal thickening of the vascular wall with fibrosis, calcification, and enforcement of the astrocyte interface with vessels with anchorage densities associated with hemidesmosome-like structures.
• In moderately and severely affected cases, fragmentation and removal of calcified and occluded vessels result in local reduction of vascular network.
• In two AD subjects, severe vascular calcification extending from the tail to the head of the hippocampal formation was associated with loss of almost all neurons in the CA1 sector and in the subiculum proper, corresponding to hippocampal sclerosis.
• Hippocampal VFC appears to be a form of vascular pathology with a unique predilection for the middle hippocampal artery and corresponding capillary network, which results in patchy neuronal loss in moderately affected subjects and in almost total neuronal loss in the area of impaired blood supply in severely affected subjects.

Why it matters

This autopsy study found vascular fibrosis and calcification in the hippocampus in some control, Alzheimer disease and Down syndrome subjects, with severe calcification linked to neuron loss in two Alzheimer cases. It describes blood vessel changes after death and provides no treatment, cure or prevention.

Study details

• Participants82
• Evidence strengthModerate

Read the original

• DOI: 10.1007/s00401-001-0471-y
• PubMed: 11904752
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

@article{wegiel2002-11904752,
  author  = {Wegiel, J. and Kuchna, I. and Wisniewski, T. and de Leon, M. J. and Reisberg, B. and Pirttila, T. and Kivimaki, T. and Lehtimaki, T.},
  title   = {{Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down syndrome}},
  journal = {Acta neuropathologica},
  year    = {2002},
  doi     = {10.1007/s00401-001-0471-y},
  pmid    = {11904752},
  url     = {https://doi.org/10.1007/s00401-001-0471-y}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Neuropathological stageing of Alzheimer-related changes Acta Neuropathologica · 1991-09-01 · usefulness score 58/100 · Brain tissue and pathology
• The Global Deterioration Scale for assessment of primary degenerative dementia The American journal of psychiatry · 1982-09-01 · usefulness score 54/100 · Getting a diagnosis
• Hippocampal sclerosis: a common pathological feature of dementia in very old (> or = 80 years of age) humans Acta neuropathologica · 1994-01-01 · usefulness score 46/100 · Brain tissue and pathology
• Neuronal loss and beta-amyloid removal in the amygdala of people with Down syndrome Neurobiology of aging · 1999-05-01 · usefulness score 34/100 · Down syndrome and Alzheimer's

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