# Impact of sleep apnea and its treatment on memory and tau accumulation in the brain

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $660,400

## Abstract

Project Summary
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by the
accumulation of tau tangles and amyloid plaques. Current consensus is that the AD pathological process begins
decades before overt clinical symptoms occur. Emerging evidence suggests that sleep disruption may be an
important factor in both early cognitive deterioration leading to AD and in the metabolism of amyloid and tau.
Obstructive sleep apnea (OSA) is the most common sleep disorder in the US with an estimated prevalence of
40-50% in the cognitively normal elderly. We have previously shown that OSA severity is associated with
longitudinal increase in brain amyloid load, but less is known about the long-term effects of OSA on tau and its
hyperphosphorylation, a crucial step in the formation of tangles, as well as the effects of OSA on spatial
navigational memory, perhaps the earliest form of memory affected in AD. Our preliminary cross-sectional
data suggest that higher OSA severity is associated with higher levels of total tau (T-tau) and phosphorylated
tau (P-tau) in the cerebrospinal fluid (CSF) and poorer overnight processing of spatial navigational memory in
cognitively normal elderly. Further, self-reported presence of OSA is associated with greater longitudinal
increase in CSF T-tau and P-tau over 3 years. Although these observations implicate OSA in aberrant memory
processing and regulation of tau in the brain, a causal role for OSA in these processes would be strengthened by
additional analyses. By measuring behavioral readouts of both the encoding and processing of spatial
navigation memory, and quantifying brain tau burden with precise anatomical resolution by adding tau PET
brain imaging at baseline and 2.5 years later in 60 asymptomatic, cognitively normal older individuals with a
wide range of OSA severity who are already being followed with polysomnography (PSG), actigraphy, and
structural brain MRI as part of R01AG056031, we can test the expectations that overnight processing of spatial
memory declines longitudinally (Aim 1) and that brain tau burden increases longitudinally (Aim 2) in a way
that is dependent on measured OSA severity. A role for OSA in the metabolism of tau also would be
strengthened by treating OSA with positive airway pressure (PAP). Whereas CSF Aβ42 levels can change in a
matter of hours depending on sleep condition, CSF tau levels are thought to change over several weeks.
Therefore, we aim to examine T-tau and P-tau in CSF and T-tau in plasma prior to treatment and 8 weeks later
in 80 cognitively normal older individuals with OSA and subjective sleepiness prescribed PAP treatment for the
first time at the Mount Sinai Integrative Sleep Center (MSISC). Satisfactory PAP adherence occurs in typically
50% of patients at the MSISC, and we will monitor adherence through downloads from users' machines.
Measuring CSF and plasma tau as a function of PAP adherence serves as the basis for Aim 3.

## Key facts

- **NIH application ID:** 10380657
- **Project number:** 5R01AG066870-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Ricardo S Osorio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $660,400
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380657

## Citation

> US National Institutes of Health, RePORTER application 10380657, Impact of sleep apnea and its treatment on memory and tau accumulation in the brain (5R01AG066870-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380657. Licensed CC0.

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