Alz Res Therapy: Hereditary dementia, the regional distribution of tau protein is highly correlated with cognitive decline

Alzheimer's disease (AD) is characterized by the presence of amyloid-β (Aβ) and tau lesions, which are thought to accumulate for many years in the preclinical stage, leading to the neurodegeneration and cognitive decline observed in the clinical stage
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Mutations in the Presenilin-1 (PSEN1; OMIM 104311) gene make individuals susceptible to autosomal dominant Alzheimer's disease (ADAD) in early adulthood, showing pathological and neurodegenerative changes similar to late-onset or sporadic AD

prevention

Positron emission tomography (PET) has achieved the in vivo characteristics and continuous tracking of Aβ and tau accumulation
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The results of the Tau PET study of sporadic AD are consistent with the spatiotemporal progression of Tauopathy implied by postmortem studies; that is, cortical Tau accumulation begins in the medial temporal lobe (MTL) distribution cortex, and then spreads with Aβ to the temporal and extratemporal neocortex ( Also called "isocortex")

Another ADAD study found that tau PET was only elevated in impaired individuals, and suggested that MTL tauopathy, including EC, may be less involved in ADAD compared with sporadic AD

Longitudinal PET studies have demonstrated pathological changes in fragile sporadic AD populations, but in ADAD, longitudinal measurements of tau and Aβ PET, and measurements of brain structure and cognitive function have not been reported
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But in ADAD, the longitudinal measurement of tau and Aβ PET, as well as the measurement of brain structure and cognitive function have not been reported
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Justin S.

Sanchez and others of Harvard University tracked young PSEN1 E280A mutation carriers and age-matched non-carriers for tau and Aβ PET measurements, and brain structure magnetic resonance imaging (MRI) measurements and recognition within 2-4 years.
Knowing the changes in the assessment, these are all from the Colombian ADAD population

They assessed the difference in the rate of change of biomarkers between carriers and non-carriers, as well as the associations between age, Aβ and tau accumulation rates, neurodegeneration, and cognitive decline
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We hypothesize that these longitudinal measures will reveal a series of changes in ADAD, starting with Aβ accumulation, followed by EC tau, neocortical tau, neurodegeneration, and cognitive decline

14 ADAD mutation carriers (Presenilin-1 E280A) and 15 age-matched non-carriers from Colombia received 2-3 Aβ (11C-Pittsburgh compound B) and tau (18F) during a 2-4 year follow-up period.

-flortaucipir) PET, structural magnetic resonance imaging and neuropsychological evaluation

The longitudinal measurement results are consistent with the order of ADAD-related changes, starting with Aβ accumulation (16 years before the onset of expected symptoms, EYO)

The accumulation rate of tau in carriers is the fastest in the parietal neocortex (about 9%/year)
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The baseline EC tau PET signal is an important factor in predicting the subsequent accumulation of neocortical tau and cognitive decline in the carrier

This study is consistent with the biological sequence of ADAD suggested by the cross-sectional study, and emphasizes the importance of EC tau as an early biomarker and the potential link between Aβ burden and neocortical tau accumulation in ADAD
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This study is consistent with the biological sequence of ADAD suggested by the cross-sectional study, and emphasizes the importance of EC tau as an early biomarker

Original source:
Sanchez JS, Hanseeuw BJ, Lopera F, et al.

Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study .
Alz Res Therapy.
2021;13(1):27 .
doi:10.
1186/s13195-020-00765-5

Longitudinal amyloid and tau accumulation in autosomal dominant Alzheimer's disease: findings from the Colombia-Boston (COLBOS) biomarker study

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