Cited by 533Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer's Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes

Open access
Lippa, Carol F., Fujiwara, Hideo, Mann, David M.A., Giasson, Benoit, Baba, Minami, Schmidt, Marie L., Nee, Linda E., O'Connell, Brendan +9 more·1998·The American Journal of Pathology

Abstract

Missense mutations in the alpha-synuclein gene cause familial Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether alpha-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to alpha-, beta-, and gamma-synuclein. LBs were detected with alpha- but not beta- or gamma-synuclein antibodies in 22% of FAD brains, and alpha-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained alpha-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, alpha-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of alpha-synuclein was reduced compared with control brains. The presence of alpha-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble alpha-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/s0002-9440(10)65722-7

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Individuals with PSEN1 mutations have increased, yet heterogeneous limbic Lewy-related pathology.

    “two studies have shown that individuals with PSEN1 mutations have increased, yet heterogeneous limbic LRP [22, 25].”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]

  • Lewy-related pathology (LRP), primarily comprised of αSyn, is present in a majority of autopsied Alzheimer's disease brains.

    “co-morbid αSyn pathology has been reported in more than half of all autopsy-confirmed AD cases [22–24]”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]

  • Co-morbid αSyn pathology has been reported in more than half of all autopsy-confirmed Alzheimer's disease cases.

    “co-morbid αSyn pathology has been reported in more than half of all autopsy-confirmed AD cases [22–24]”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [22]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 35 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Foncin JF, Salmon D, Supino-Viterbo V, Feldman RG, Macchi G, Mariotti P, Scoppeta C, Caruso G, Bruni AC: Demence presenile d'Alzheimer transmise'dans une famille etendue. Rev Neurol (Paris) 1985, 141:194 -202
  2. Nochlin D, Bird TD, Nemens EJ, Ball MJ, Sumi SM: Amyloid angiop- athy in a Volga German family with Alzheimer's disease and a PS-2 mutation (N1411). Ann Neurol 1998, 43:131-135

Cited by

Sorted by citations

Authors
Lippa, C. F., Fujiwara, H., Mann, D. M. A., Giasson, B., Baba, M., Schmidt, M. L., Nee, L. E., O'Connell, B., Pollen, D. A., St. George-Hyslop, P., Ghetti, B., Nochlin, D., Bird, T. D., Cairns, N. J., Lee, V. M.-Y., Iwatsubo, T., & Trojanowski, J. Q.
Affiliations
  • The University of Tokyo (JP)
  • University of Manchester (GB)
  • University of Pennsylvania (US)
  • National Institute of Neurological Disorders and Stroke (US)
  • University of Massachusetts Chan Medical School (US)
  • Indiana University Hospital (US)
  • University of Washington (US)
Corresponding author
Lippa, Carol F.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
1998-11
Volume
153
Issue
5
Pages
1365-1370
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2066155243
Cited by
533
References
35
Citations by year
2026: 10 · 2025: 17 · 2024: 23 · 2023: 16 · 2022: 19 · 2021: 21 · 2020: 19 · 2019: 17 · 2018: 16 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 25 · 2013: 13 · 2012: 11
FWCI
17.79
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (7r29ag013623-06)
  • National Institute on Aging (P30AG010133, AG09215, U01AG006781, AG13623, P30AG010124, P01AG009215, AG-10124, P50AG005136)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Lewy bodies, alpha-synuclein, familial Alzheimer's disease, presenilin mutations, amyloid precursor protein mutations, amygdala, alpha-synuclein aggregation, protein insolubility, immunoelectron microscopy
MeSH terms
Adult, Aged, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Middle Aged, Mutation, Nerve Tissue Proteins, Blotting, Western, Microscopy, Immunoelectron, Amyloid beta-Protein Precursor, Lewy Bodies, Synucleins, alpha-Synuclein, gamma-Synuclein, Presenilin-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review