Genotype-phenotype relationships of presenilin-1 mutations in Alzheimer's disease: An update
Abstract
It is now more than ten years since pathogenic mutations were first described in the gene encoding presenilin 1 (PSEN1) on chromosome 14. Although PSEN1 mutations are "deterministic" for Alzheimer's disease, they are associated with marked heterogeneity in the clinical expression of neurological features. We review recent publications on the clinical neurological phenotype of PSEN1 mutations, many of which now appear only in abstracts or brief communications, perhaps because PSEN1 mutations are no longer regarded as "novel". However, the clinical heterogeneity associated with these mutations prompts important questions about possible genetic and epigenetic factors which may modify disease phenotype. This area, which may also be relevant to neurodegenerative disorders resulting from other genetic mutations, such as those in the tau gene, currently remains ill-understood.
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Phenotype is not rigidly linked to etiology and may be moldable to a large extent by an individual's genetic and epigenetic background and/or total environmental exposure.
“These findings suggest that phenotype is not rigidly linked to etiology and may be moldable to a large extent by an individual's genetic and epigenetic background and/or total environmental exposure.”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [45]
Correlation studies between molecular genetics and neuropathology indicate that for several autosomal dominant dementias, the presenting clinical phenotype may vary widely, from various dementia subtypes to parkinsonism to motor neuron disease-like, even among individuals with the same causative mutation.
“Correlation studies between molecular genetics and neuropathology also indicate that for several autosomal dominant dementias, the presenting clinical phenotype may vary widely, from various dementia subtypes to parkinsonism to motor neuron disease-like, even among individuals with the same causative mutation (44-47).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [45]
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References 50 · Cited by 67
- Authors
- Larner, A. J., & Doran, M.
- Affiliations
- Walton Centre (GB)
- Corresponding author
- Larner, Andrew J.
- ORCID
- Larner, Andrew J.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2008-11-16
- Volume
- 17
- Issue
- 2
- Pages
- 259-265
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2162081270
- Cited by
- 67
- References
- 50
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 6 · 2016: 4 · 2015: 3 · 2014: 8 · 2013: 14 · 2012: 5
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- 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
- presenilin 1, PSEN1 mutations
- MeSH terms
- Alzheimer Disease, Genotype, Humans, Mutation, Phenotype, Genetic Predisposition to Disease, Presenilin-1
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