Common genetic variation is associated with longitudinal decline and network features in behavioral variant frontotemporal degeneration
Open accessAbstract
The T allele in rs1768208 located in or near the myelin oligodendrocyte basic protein gene (MOBP) is a risk factor for frontotemporal degeneration pathology. We evaluated the hypothesis that the presence of a T allele in rs1768208 will be associated with rate of cognitive decline in behavioral variant frontotemporal degeneration (bvFTD) related to compromised frontal networks. We studied 81 individuals clinically diagnosed with bvFTD who were genotyped for rs1768208 and coded using a dominant model reflecting the presence (i.e., MOBP +) or absence (MOBP -) of the T risk allele. Linear mixed-effects models assessed the association of genotype on neuropsychological performance over time. Regression analyses examined differences in network structure by MOBP genotype. We found a genotype by time interaction for declining cognitive performance, whereby MOBP + individuals demonstrated faster rates of decline in executive function. The presence of a MOBP risk allele was associated with degradation of white matter network features in the frontal lobe. These findings suggest that individual genetic variation may contribute to heterogeneity in clinical progression.
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White matter pathology has been correlated with the presence of a MOPB-risk allele.
“the presence of a MOPB-risk allele (Massimo et al., 2021)”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Massimo et al., 2021
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Self-citation
- Authors
- Massimo, L., Rennert, L., Xie, S. X., Olm, C., Bove, J., Van Deerlin, V., Irwin, D. J., Grossman, M., & McMillan, C. T.
- Affiliations
- University of Pennsylvania (US)
- Clemson University (US)
- Corresponding author
- Massimo, Lauren
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 108
- Pages
- 16-23
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC8616801
- OpenAlex
- W3188090963
- Cited by
- 6
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 1 · 2019: 1
- FWCI
- 0.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Biogen
- National Institutes of Health (AG052943, AG056054, AG066597, AG17586)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- MOBP, risk alleles, cognitive decline, executive function
- MeSH terms
- Aged, Alleles, Brain, Cognition, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Myelin Proteins, Polymorphism, Single Nucleotide, Executive Function, Genetic Association Studies, Frontotemporal Dementia, Neuroimaging, White Matter
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