Alzheimer's research & therapy
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Alzheimers Res Ther · Feb 2021
Genetically determined blood pressure, antihypertensive medications, and risk of Alzheimer's disease: a Mendelian randomization study.
Observational studies suggest that the use of antihypertensive medications (AHMs) is associated with a reduced risk of Alzheimer's disease (AD); however, these findings may be biased by confounding and reverse causality. We aimed to explore the effects of blood pressure (BP) and lowering systolic BP (SBP) via the protein targets of different AHMs on AD through a two-sample Mendelian randomization (MR) approach. ⋯ This MR analysis found evidence that genetically determined lowering BP was associated with a lower risk of AD and CCB was identified as a promising strategy for AD prevention.
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Alzheimers Res Ther · Jan 2021
Observational StudyAlzheimer's cerebrospinal biomarkers from Lumipulse fully automated immunoassay: concordance with amyloid-beta PET and manual immunoassay in Koreans : CSF AD biomarkers measured by Lumipulse in Koreans.
Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans. ⋯ CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Aβ-PET in Koreans. The Korean-specific Aβ-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts.
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Alzheimers Res Ther · Jan 2021
Association between polygenic risk score of Alzheimer's disease and plasma phosphorylated tau in individuals from the Alzheimer's Disease Neuroimaging Initiative.
Recent studies suggest that plasma phosphorylated tau181 (p-tau181) is a highly specific biomarker for Alzheimer's disease (AD)-related tau pathology. It has great potential for the diagnostic and prognostic evaluation of AD, since it identifies AD with the same accuracy as tau PET and CSF p-tau181 and predicts the development of AD dementia in cognitively unimpaired (CU) individuals and in those with mild cognitive impairment (MCI). Plasma p-tau181 may also be used as a biomarker in studies exploring disease pathogenesis, such as genetic or environmental risk factors for AD-type tau pathology. The aim of the present study was to investigate the relation between polygenic risk scores (PRSs) for AD and plasma p-tau181. ⋯ Polygenic risk for AD including APOE was found to associate with plasma p-tau181 independent of diagnostic and Aβ pathology status, while polygenic risk for AD beyond APOE was associated with plasma p-tau181 only in MCI and Aβ-positive individuals. These results extend the knowledge about the relation between genetic risk for AD and p-tau181, and further support the usefulness of plasma p-tau181 as a biomarker of AD.
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Alzheimers Res Ther · Sep 2020
Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: a nationally representative cohort study.
Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. ⋯ These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.
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Alzheimers Res Ther · Aug 2020
ReviewAducanumab, gantenerumab, BAN2401, and ALZ-801-the first wave of amyloid-targeting drugs for Alzheimer's disease with potential for near term approval.
The body of evidence suggesting a causative, initiating role of beta amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD) is substantial. Yet, only a few anti-amyloid agents have shown meaningful efficacy in clinical trials. We evaluated the unifying characteristics of anti-amyloid agents with positive clinical or biomarker effects in long-duration trials and analyzed how pharmacological characteristics determine their clinical product profiles. ⋯ The most advanced selective anti-oligomer agent is ALZ-801, an optimized oral prodrug of tramiprosate, which demonstrated efficacy in homozygous APOE4/4 AD subjects. ALZ-801 selectively and fully inhibits the formation of Aβ42 oligomers at the clinical dose, without evidence of vasogenic edema, and will be evaluated in a phase 3 trial in homozygous APOE4/4 patients with early AD. In addition to clinical measures, the phase 3 trial will include cerebrospinal fluid, plasma, and imaging biomarkers to gain further insights into the role of soluble Aβ oligomers in the pathogenesis of AD and their impact on disease progression.