UNDERSTANDING THE MECHANISTIC LINK BETWEEN VASCULAR DYSFUNCTION AND ALZHEIMERS DISEASE-RELATED PROTEIN ACCU…

Assistance award details

Assistance award identifier

ASST_NON_R00AG080134_075

FAIN

R00AG080134

Recipient

THE GENERAL HOSPITAL CORPORATION

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$493,020

Period

Aug 15, 2023 – Jun 30, 2028

Fiscal year

2025

Place of performance state

MA

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

UNDERSTANDING THE MECHANISTIC LINK BETWEEN VASCULAR DYSFUNCTION AND ALZHEIMERS DISEASE-RELATED PROTEIN ACCUMULATION IN THE MEDIAL TEMPORAL LOBE - PROJECT SUMMARY/ABSTRACT TITLE: UNDERSTANDING THE MECHANISTIC LINK BETWEEN VASCULAR DYSFUNCTION AND ALZHEIMER’S DISEASE-RELATED PROTEIN ACCUMULATION IN THE MEDIAL TEMPORAL LOBE. CEREBRAL SMALL VESSEL DISEASE (CSVD), WHICH AFFECTS SMALL VESSELS OF THE BRAIN IN THE FORM OF CEREBRAL AMYLOID ANGIOPATHY (CAA) OR ARTERIOLOSCLEROSIS, IS EITHER PRIMARILY RESPONSIBLE OR A SIGNIFICANTLY CONTRIBUTING FACTOR TO ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (AD/ADRD). HOWEVER, IT REMAINS UNCLEAR WHETHER VASCULAR PATHOLOGY AND AD-RELATED PATHOLOGY INDEPENDENTLY CONTRIBUTE TO DEMENTIA OR CAUSALLY INTERACT WITH EACH OTHER. DYSFUNCTION IN PERIVASCULAR CLEARANCE, ONE OF THE SYSTEMS RESPONSIBLE FOR THE DISPOSAL OF METABOLIC WASTE PRODUCTS FROM THE BRAIN, AND BLOOD-BRAIN BARRIER (BBB) LEAKAGE, BOTH OCCUR WHEN CSVD PATHOLOGY IS PRESENT AND ARE CANDIDATE MECHANISMS THAT COULD EXPLAIN THIS INTERACTION. THE OBJECTIVE OF THE PROPOSED RESEARCH IS TO PINPOINT THE RECIPROCAL INTERACTION BETWEEN CSVD AND AD-RELATED PATHOLOGY, IN ORDER TO INFER ITS UNDERLYING MECHANISMS. THE FOCUS WILL BE ON THE MEDIAL TEMPORAL LOBE (MTL), A CRITICAL BRAIN REGION FOR THE DEVELOPMENT OF AD/ADRD, BECAUSE IT IS FUNDAMENTAL FOR COGNITION AND IT IS A SITE WHERE A MULTIPLICITY OF AD-RELATED PATHOLOGIES COEXIST (E.G. AΒ-PLAQUES, NEUROFIBRILLARY TAU TANGLES, TAR DNA BINDING PROTEIN 43, AND NEURONAL LOSS), SOME OF WHICH IN VERY EARLY STAGES OF THE DISEASE (E.G. TANGLES). FIRSTLY, THE APPLICANT WILL INVESTIGATE WHETHER CSVD IN THE MTL WORSENS AD-RELATED PATHOLOGY (HYPOTHESIS 1). SECONDLY, SHE WILL INFER THE CONTRIBUTING ROLE OF PERIVASCULAR CLEARANCE DYSFUNCTION AND BBB-LEAKAGE TO THESE INTERACTIONS (HYPOTHESIS 2) AND AIMS TO CREATE AND VALIDATE NEUROIMAGING MARKERS OF MICROVASCULAR HEALTH IN THE MTL (HYPOTHESIS 3). THE INNOVATION OF THIS PROPOSAL LIES IN THE USE OF QUANTITATIV