# Individual Differences in Obstructive Sleep Apnea > **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $387,854 ## Abstract ABSTRACT Sleep disturbances with reduced amounts of sleep and sleep fragmentation are common in Alzheimer’s disease. These sleep abnormalities occur before the onset of cognitive impairments. This also occurs in mouse models of Alzheimer’s disease in mice in whom the mutations of genes that are responsible for familial Alzheimer’s disease are knocked in. These sleep abnormalities are not just a consequence of the disease process but likely also accelerate disease progression. The responsible A42 is released from neurons in the brain during wakefulness. This reduction in sleep and increase in wakefulness give more time over the 24 hour period for increased production of A42. Moreover, the protein  amyloid that aggregates in plaques in Alzheimer’s disease is more rapidly cleared from the brain during sleep. Thus, study of sleep abnormalities in Alzheimer’s disease are important to understanding the pathogenesis of disease. While much has been learned about Alzheimer’s disease from studies of mouse models, these models lack the genetic heterogeneity found in the human population. Recently a new approach in mice has been developed. Mice carrying mutations that are responsible for Alzheimer’s disease are bred with a panel of recombinant inbred lines creating multiple different lines of mice that are genetically driven but all carry the same mutations for Alzheimer’s disease. Some of these mouse lines are very resistant to developing cognitive deficits, while others are very sensitive. Moreover, initial studies show that there is also a variation in the onset of sleep abnormalities in these diverse mouse lines. This variation gives the opportunity to identifying modifier genes that alter the timing of the onset of sleep abnormalities. One potential modifier gene has already been identified. Building on this initial observation we propose to study sleep in more of these lines. We will conduct in-depth phenotyping of multiple lines at different ages and assess sleep amounts, sleep fragmentation, vigilance (latency to sleep in a new environment), and circadian behavior using wheel running. These data will be used to identify additional modifier genes. Studying an increasing number of these lines increases the power of the study and provides more precision for mapping and identifying genes. In addition, we will assess with EEG/EMG recording whether one modifier gene already identified does indeed affect sleep. Identifying modifier genes that slow the rate of progression of disease could provide new targets for pharmacological intervention. ## Key facts - **NIH application ID:** 10123864 - **Project number:** 3P01HL094307-10S1 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** Allan I Pack - **Activity code:** P01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $387,854 - **Award type:** 3 - **Project period:** 2009-07-01 → 2022-04-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10123864 ## Citation > US National Institutes of Health, RePORTER application 10123864, Individual Differences in Obstructive Sleep Apnea (3P01HL094307-10S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10123864. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*