ArticleMolecular neurodegeneration2008
Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations.
Article in Molecular neurodegeneration, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
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- Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology.Brain : a journal of neurology · 2022Article
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- Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2022Article
- Variant-dependent heterogeneity in amyloid β burden in autosomal dominant Alzheimer's disease: cross-sectional and longitudinal analyses of an observational study.The Lancet. Neurology · 2022Observational
- Cryo-EM structures of amyloid-β 42 filaments from human brains.Science (New York, N.Y.) · 2022Article
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- Patient-Derived Fibroblasts With Presenilin-1 Mutations, That Model Aspects of Alzheimer's Disease Pathology, Constitute a Potential Object for Early Diagnosis.Frontiers in aging neuroscience · 2022Article
- Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease.Acta neuropathologica · 2021Observational
- Thiophene-Based Optical Ligands That Selectively Detect Aβ Pathology in Alzheimer's Disease.Chembiochem : a European journal of chemical biology · 2021Article
- Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer's Disease.International journal of molecular sciences · 2021Article
- Amyloid in the ageing brain: New frameworks and perspectives.Aging brain · 2021Article
- Identification of Multicolor Fluorescent Probes for Heterogeneous Aβ Deposits in Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- Contributions of Molecular and Optical Techniques to the Clinical Diagnosis of Alzheimer's Disease.Brain sciences · 2020Review
- Molecular subtypes of Alzheimer's disease.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundMutations in the presenilin (PSEN) genes are associated with early-onset familial Alzheimer's disease (FAD). Biochemical characterizations and comparisons have revealed that many PSEN mutations alter gamma-secretase activity to promote accumulation of toxic Abeta42 peptides. In this study, we compared the histopathologic and biochemical profiles of ten FAD cases expressing independent PSEN mutations and determined the degradation patterns of amyloid-beta precursor protein (AbetaPP), Notch, N-cadherin and Erb-B4 by gamma-secretase. In addition, the levels of Abeta40/42 peptides were quantified by ELISA.
resultsWe observed a wide variation in type, number and distribution of amyloid deposits and neurofibrillary tangles. Four of the ten cases examined exhibited a substantial enrichment in the relative proportions of Abeta40 over Abeta42. The AbetaPP N-terminal and C-terminal fragments and Tau species, assessed by Western blots and scanning densitometry, also demonstrated a wide variation. The Notch-1 intracellular domain was negligible by Western blotting in seven PSEN cases. There was significant N-cadherin and Erb-B4 peptide heterogeneity among the different PSEN mutations.
conclusionThese observations imply that missense mutations in PSEN genes can alter a range of key gamma-secretase activities to produce an array of subtly different biochemical, neuropathological and clinical manifestations. Beyond the broad common features of dementia, plaques and tangles, the various PSEN mutations resulted in a wide heterogeneity and complexity and differed from sporadic AD.
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