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Basic Science and Pathogenesis.

Taylor W Schmitz1

  • 1Schulich Medicine and Dentistry, London, ON, Canada; Robarts Research Institute, London, ON, Canada.

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This study uses touchscreen cognitive tests in humans and mice to understand Alzheimer's disease (AD) mechanisms. Findings may reveal how genetic risk factors like ApoE influence early cognitive decline.

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Area of Science:

  • Neuroscience
  • Genetics
  • Cognitive Science

Background:

  • Cross-species translation of cognitive testing is vital for Alzheimer's disease (AD) research.
  • Mouse models provide mechanistic insights into cognitive decline influenced by genetic and biological factors.
  • Touchscreen cognitive tasks enable consistent testing in humans and mice, bridging preclinical and clinical research.

Purpose of the Study:

  • To integrate homologous touchscreen cognitive tests in parallel studies of AD mouse models and humans at risk for AD.
  • To explore how genetic factors (amyloid, tau, ApoE) interact with age and sex in executive function using the Continuous Performance Task (CPT).
  • To investigate the role of touchscreen cognitive testing in elucidating AD risk mechanisms and early cognitive dysfunction.

Main Methods:

  • Leveraging an ongoing collaboration between Western and McGill Universities.
  • Utilizing next-generation AD mouse models with humanized knock-in genes.
  • Integrating the Continuous Performance Task (CPT), a touchscreen-based selective attention probe, into the longitudinal PREVENT-AD human study.

Main Results:

  • The PREVENT-AD study, including over 425 individuals at risk for AD, has integrated CPT testing.
  • Longitudinal CPT data has been acquired from approximately 80 participants in the PREVENT-AD cohort.
  • Mouse models with humanized ApoE genotypes are being used to study executive function.

Conclusions:

  • Touchscreen-based cognitive testing in humans and mice can elucidate AD risk mechanisms.
  • PREVENT-AD and mouse CPT data may reveal interactions between ApoE genotype, age, and sex in early cognitive dysfunction.
  • Touchscreen tests may offer enhanced sensitivity to early AD-related cognitive decline compared to standard neuropsychological tests.