Cited by 184Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43)

Mann, D. M. A., Iwatsubo, T., Cairns, N. J., Lantos, P. L., Nochlin, D., Sumi, S. M., Bird, T. D., Poorkaj, P. +6 more·1996·Annals of Neurology

Abstract

Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of 8 cases of (genetically confirmed) chromosome 14-linked Alzheimer's disease (AD) using the end-specific monoclonal antibodies BA27 and BC05 to detect the presence of Abeta40 and Abeta42(43), respectively. In all patients, Abeta42(43) was the predominant peptide species present. The total amount of Abeta40 and Abeta42(43) deposited was more than twice the amount deposited in cases of sporadic AD of similar disease duration, although the ratio between the extent of Abeta40 and Abeta42(43) deposition was unaltered, compared with sporadic AD. Therefore, (one of) the effects of the mutations in the presenilin 1:PS-1 (S182) gene may be to cause or at least promote an early and excessive deposition of Abeta42(43) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).

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Crossref · 10.1002/ana.410400205

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  • Human PSEN1 mutation carriers have notable BBB breakdown and cerebrovascular dysfunction including cerebellar amyloid angiopathy and CAA, disrupted meningeal, subpial, and cortical arterioles, degeneration of pericytes and SMCs, cerebral perivascular amyloid deposits, and diminished FDG transport across the BBB in an early asymptomatic stage.

    “Human PSEN1 mutation carriers have notable BBB breakdown and cerebrovascular dysfunction including cerebellar amyloid angiopathy and CAA (143, 183, 274, 280, 354, 389, 440, 500, 544, 573, 639, 668); disrupted meningeal, subpial, and cortical arterioles (274, 389, 440); degeneration of pericytes and SMCs (573); cerebral perivascular amyloid deposits (25, 274, 289, 354, 573, 668); and diminished FDG”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [389]

  • Cerebrovascular pathology with BBB breakdown was shown by neuropathological studies in patients with specific PSEN1 mutations including T113-114 insertion, P117L, M139V, M146V, L153V, H163R, E184D, G209V, A260V, C260T, E280A, L282V, C285T, L420R, and Δe9 deletion.

    “Particularly, cerebrovascular pathology with BBB breakdown was shown by neuropathological studies in patients with PSEN1 T113-114 insertion (544), P117L (573, 639), M139V (183, 389), M146V (389), L153V (289), H163R (280), E184D (668), G209V (389), A260V (389), C260T (274), E280A (354), L282V (143), C285T (274), and L420R (440) missense mutations, and 𝚫 e9 deletion (280).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [389]

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Authors
Mann, D. M. A., Iwatsubo, T., Cairns, N. J., Lantos, P. L., Nochlin, D., Sumi, S. M., Bird, T. D., Poorkaj, P., Hardy, J., Hutton, M., Prihar, G., Crook, R., Rossor, M. N., & Haltia, M.
Affiliations
  • University of Manchester (GB)
  • The University of Tokyo (JP)
  • University of Washington (US)
  • University of South Florida (US)
  • National Hospital for Neurology and Neurosurgery (GB)
  • University of Helsinki (FI)
Corresponding author
Mann, D. M. A.
Venue
Annals of Neurology
Publisher
Wiley
Published
1996-08
Volume
40
Issue
2
Pages
149-156
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2076606883
Cited by
184
References
36
Citations by year
2026: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
15.51
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG 05136, U01AG006781, AG06781-06, P50AG005136)
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
amyloid-beta, Aβ40, presenilin 1 mutations, frontal cortex, amyloid deposition, sporadic Alzheimer's disease, familial Alzheimer's disease, Down syndrome, amyloid precursor protein mutations
MeSH terms
Adult, Alzheimer Disease, Antibodies, Monoclonal, Apolipoproteins E, Chromosomes, Human, Pair 14, Female, Frontal Lobe, Humans, Male, Membrane Proteins, Middle Aged, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, Point Mutation, Presenilin-1

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