ArticleActa neuropathologica2012
The MAPT H1 haplotype is associated with tangle-predominant dementia.
Article in Acta neuropathologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 82 citations in OpenAlex.
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- Primary age-related tauopathy.Acta neuropathologica · 2025Review
- Hippocampal tau distribution in primary age-related tauopathy: The Vantaa 85+ Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Amyloid-β predominant Alzheimer's disease neuropathologic change.Brain : a journal of neurology · 2025Article
- MAPT haplotype-associated transcriptomic changes in progressive supranuclear palsy.Acta neuropathologica communications · 2024Article
- Prevalence and clinicopathological features of primary age-related tauopathy (PART): A large forensic autopsy study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The clinical importance of suspected non-Alzheimer disease pathophysiology.Nature reviews. Neurology · 2024Review
- Genetic forms of tauopathies: inherited causes and implications of Alzheimer's disease-like TAU pathology in primary and secondary tauopathies.Journal of neurology · 2024Review
- Histopathologic brain age estimation via multiple instance learning.Acta neuropathologica · 2023Article
- The relationship between hippocampal amyloid beta burden and spatial distribution of neurofibrillary degeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Cognitive and Neuropsychological Profiles in Alzheimer's Disease and Primary Age-Related Tauopathy and the Influence of Comorbid Neuropathologies.Journal of Alzheimer's disease : JAD · 2023Article
- The Adult Neurogenesis Theory of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Towards an understanding of the pathological basis of senile depression and incident dementia: Implications for treatment.Psychiatry and clinical neurosciences · 2022Review
- Differential Vulnerability of Hippocampal Subfields in Primary Age-Related Tauopathy and Chronic Traumatic Encephalopathy.Journal of neuropathology and experimental neurology · 2022Article
- TargetingInternational journal of molecular sciences · 2022Article
- Primary age-related tauopathy in a Finnish population-based study of the oldest old (Vantaa 85+).Neuropathology and applied neurobiology · 2022Article
- Identification of recurrent genetic patterns from targeted sequencing panels with advanced data science: a case-study on sporadic and genetic neurodegenerative diseases.BMC medical genomics · 2022Article
- Genome-wide association study and functional validation implicates JADE1 in tauopathy.Acta neuropathologica · 2022Article
- Alzheimer's disease is an inherent, natural part of human brain aging: an integrated perspective.Free neuropathology · 2022Article
- Tau and MAPT genetics in tauopathies and synucleinopathies.Parkinsonism & related disorders · 2021Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Tangle-predominant dementia (TPD) patients exhibit cognitive decline that is clinically similar to early to moderate-stage Alzheimer disease (AD), yet autopsy reveals neurofibrillary tangles in the medial temporal lobe composed of the microtubule-associated protein tau without significant amyloid-beta (Aβ)-positive plaques. We performed a series of neuropathological, biochemical and genetic studies using autopsy brain tissue drawn from a cohort of 34 TPD, 50 AD and 56 control subjects to identify molecular and genetic signatures of this entity. Biochemical analysis demonstrates a similar tau protein isoform composition in TPD and AD, which is compatible with previous histological and ultrastructural studies. Further, biochemical analysis fails to uncover elevation of soluble Aβ in TPD frontal cortex and hippocampus compared to control subjects, demonstrating that non-plaque-associated Aβ is not a contributing factor. Unexpectedly, we also observed high levels of secretory amyloid precursor protein α (sAPPα) in the frontal cortex of some TPD patients compared to AD and control subjects, suggesting differences in APP processing. Finally, we tested whether TPD is associated with changes in the tau gene (MAPT). Haplotype analysis demonstrates a strong association between TPD and the MAPT H1 haplotype, a genomic inversion associated with some tauopathies and Parkinson disease (PD), when compared to age-matched control subjects with mild degenerative changes, i.e., successful cerebral aging. Next-generation resequencing of MAPT followed by association analysis shows an association between TPD and two polymorphisms in the MAPT 3' untranslated region (UTR). These results support the hypothesis that haplotype-specific variation in the MAPT 3' UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD.
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