Cited by 96Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAmyotrophic Lateral Sclerosis Research

Genetic Heterogeneity in Alzheimer Disease and Implications for Treatment Strategies

Open access
Dominantly Inherited Alzheimer Network, Ringman, John M., Goate, Alison, Masters, Colin L., Cairns, Nigel J., Danek, Adrian, Graff-Radford, Neill, Ghetti, Bernardino +1 more·2014·Current Neurology and Neuroscience Reports

Abstract

Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer's disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses.

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 · 10.1007/s11910-014-0499-8

Cites

95 of 95 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?

  • Mutations in both APP and PSEN1 cause aberrant APP cleavage and clearance that lead to neuroinflammation, activation of astrocytes and microglia, and changes in bioenergetics.

    “Mutations in both APP and PSEN1 cause aberrant APP cleavage and clearance4,47 that lead to neuroinflammation, the activation of astrocytes and microglia, and changes in bioenergetics44,48.”

    From Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice (2026) · cites this paper as [4]

    The 'Amyloid Precursor Protein' and 'The Presenilins' sections (pages not supplied) describe how APP and PSEN1 mutations alter APP cleavage and Aβ production. The 'Autosomal dominant forms of AD' section distinguishes reduced Aβ clearance in late-onset AD from increased Aβ synthesis in PSEN1 mutation carriers; it does not establish aberrant clearance for both mutations. The later inflammation, glial-activation, and bioenergetics claims carry separate citations. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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 96 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [69]Selkoe D Kopan R Notch and presenilin: regulated intramembrane proteolysis links development and degeneration Annu Rev Neurosci 2003 26 565 97 12730322

Cited by

Sorted by citations

Authors
Dominantly Inherited Alzheimer Network, Ringman, J. M., Goate, A., Masters, C. L., Cairns, N. J., Danek, A., Graff-Radford, N., Ghetti, B., & Morris, J. C.
Affiliations
  • University of California, Los Angeles (US)
  • The University of Melbourne (AU)
  • Washington University in St. Louis (US)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Ringman, John M.
Venue
Current Neurology and Neuroscience Reports
Published
2014-09-14
Volume
14
Issue
11
Pages
499-499
ISSN
  • 1528-4042 (ISSN-L)
  • 1534-6293
OpenAlex
W2093198322
Cited by
96
References
96
Citations by year
2026: 5 · 2025: 10 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 3 · 2017: 9 · 2016: 6 · 2015: 4
FWCI
0.74
Type
journal article
Language
en
Open access
Locations
  • Current Neurology and Neuroscience Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • DZNE Pub (submittedVersion, other-oa)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
  • National Institute on Aging (AG-016570, P50AG016570, P 50 AG05681, UF1AG032438, P50AG005681, P01 AG0 3991, P01AG003991, P01AG026276)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
Alzheimer's disease, genetic heterogeneity, autosomal dominant Alzheimer's disease, PSEN1 mutations, APP mutations, PSEN2 mutations, APOE ε4, Down syndrome, preclinical Alzheimer's disease, clinical trial design, treatment response, genetic risk factors
MeSH terms
Alzheimer Disease, Animals, Humans, Membrane Proteins, Amyloid beta-Protein Precursor, Genetic Heterogeneity, Presenilin-1, Presenilin-2

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