Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanisms of Alzheimer's Disease Progression in the Aging Brain

Award Number: R01AG062542
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Mechanisms of Alzheimer's Disease Progression in the Aging Brain - PROJECT SUMMARY While late onset sporadic Alzheimer's disease (AD) is usually announced with amnesia, the aggregated proteins β-amyloid (Aβ) and tau probably deposit in the brain for many years before symptom onset. This process occurs in the brain's episodic memory system, on a background of normal aging. Increasing evidence points to the spread of the tau protein out of the medial temporal lobe and into neocortical brain regions as crucial in the transition from normal aging to AD, possibly driven by Aβ and patterns of neural activity and connectivity. In this project we will specifically examine two subsystems of the episodic memory system, an anterior temporal (AT) system originating in lateral entorhinal cortex (LEC) specialized for object memory, and a posteromedial system (PM) system originating in medial entorhinal cortex (MEC) specialized for spatial memory. This is important for differentiating aging and AD because tau deposition begins in the LEC in older brains, while Aβ deposits in the PM system. The application builds upon on a longitudinal cohort consisting of almost 200 cognitively normal older people who have previously had baseline amyloid PET scanning with [11C]PIB, longitudinal structural MRI exams, and some of whom have had tau-PET imaging with [18F]flortaucipir. For this project, 120 participants will undergo a baseline examination of PIB-PET, flortaucipir- PET, structural MRI, and neuropsychological testing of memory and other cognitive abilities; these procedures will be repeated 1.5 and 3 years later. The baseline examination will also include a functional MRI experiment in which participants encode novel objects and scenes to define the AT and PM episodic memory systems. Neural activity will be examined using directed functional connectivity (directed-FC), an analytic approach employing Granger causality with assessment of neural activity directed from one region to another. This directed-FC will model the spread of tau through memory systems over the ensuing 3 years. Aim 1 will examine the overall pattern of tau spread in relation to the presence of Aβ, longitudinal cortical atrophy, and cognitive change. We hypothesize that Aβ will speed tau spread, which in turn will be associated with atrophy and memory decline. Aim 2 will examine tau spread through the AT and PM systems. We hypothesize that tau spreads predominantly in the AT system and, as such, reflects an enhancement of the processes that begin in the aged brain and not an anatomical or functional new condition. Aim 3 will use directed-FC to predict the spread of tau over time, with the hypothesis that brain regions most strongly connected to the entorhinal cortex will show the most rapid spread of tau pathology and this will be strongest in the AT system. How tau spreads through these systems and how Aβ and neural connectivity may drive this spread could help to differentiate the earliest stages of AD from normal aging, identify normal individuals at highest risk of progression, and provide new approaches to the selection of individuals for clinical trials.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	001	5	8/20/2025	NON-COMPETING CONTINUATION	$0
2025	2023	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	5	6/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $849,165 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	5	6/12/2023	NON-COMPETING CONTINUATION	$849,165
														Subtotal = $849,165

Issue Date FY: 2022 ( Subtotal = $849,165 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	4	6/22/2022	NON-COMPETING CONTINUATION	$849,165
														Subtotal = $849,165

Issue Date FY: 2021 ( Subtotal = $848,863 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	3	6/4/2021	NON-COMPETING CONTINUATION	$848,863
														Subtotal = $848,863

Issue Date FY: 2020 ( Subtotal = $845,658 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	2	6/25/2020	NON-COMPETING CONTINUATION	$845,658
														Subtotal = $845,658

Issue Date FY: 2019 ( Subtotal = $848,137 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	001	1	9/20/2019	NEW	$0
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1 CYCLOTRON RD	BERKELEY	CA	94720	ALAMEDA	USA	Aging Research	000	1	8/9/2019	NEW	$848,137
														Subtotal = $848,137

Grand Total All Awards = $4,240,988

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of Alzheimer's Disease Progression in the Aging Brain

Award Number: R01AG062542

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer