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Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
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Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Updated: Jun 13, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
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Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease

Published on: November 14, 2017

A Favorable Modifiable Risk Factor Profile Mitigates Polygenic Risk for Alzheimer's Disease and Related Dementia.

Clayton O Mansel, Soniya Mishra, Andrew Craver

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    A healthy lifestyle significantly reduces Alzheimer

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    Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
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    A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

    Published on: July 14, 2016

    Area of Science:

    • Neuroscience
    • Genetics
    • Public Health

    Background:

    • Up to 45% of Alzheimer's Disease and Related Dementias (ADRD) may be preventable through lifestyle changes.
    • Genome-wide association studies (GWAS) highlight the role of genetic variants in ADRD risk.
    • The interplay between lifestyle and genetic predisposition for ADRD remains unclear.

    Purpose of the Study:

    • To investigate whether a favorable lifestyle can mitigate ADRD risk in genetically susceptible individuals.
    • To assess the relative contributions of modifiable risk factors and genetic factors to ADRD development.

    Main Methods:

    • Retrospective cohort study of 105,886 participants from the All of Us Research Program (2018-2023).
    • Assessed 14 modifiable ADRD risk factors using surveys, EHR, and wearable data.
    • Quantified genetic risk using a polygenic risk score (PRS) and APOE ε4 genotype.

    Main Results:

    • Ten modifiable risk factors were significantly associated with ADRD.
    • Intermediate and unfavorable lifestyle profiles substantially increased ADRD risk (HR 3.07 and 8.01, respectively).
    • A favorable lifestyle reduced ADRD risk by 90% in those with high polygenic risk, but APOE ε4 homozygotes remained at elevated risk.

    Conclusions:

    • Modifiable risk factors and APOE genotype appear to be stronger drivers of ADRD risk than polygenic risk score alone.
    • Genomic-informed ADRD risk assessments need calibration to accurately identify high-risk individuals.
    • Lifestyle interventions hold significant potential for ADRD prevention, particularly in genetically predisposed populations.