#  Davide Micheletti 

Jessie Fang Lu Fu, Ph.D.

Martinos Center for Biomedical Imaging, Dept. of Radiology, MGH, Harvard Medical School, HST/MIT

Project Title: Perfusion-Related Network Vulnerability to Early Tau Accumulation in Preclinical Alzheimer's Disease

 

 

 



   ![Davide Micheletti](/sites/g/files/omnuum5331/files/styles/hwp_4_5__320x400/public/2026-09/photo_Micheletti_0.jpg?itok=75pgpxb7) 

 



 





 

**Project Summary:** Alzheimer's disease (AD) is the most common cause of dementia, affecting millions of  
people worldwide. Although approved therapies can slow disease progression, they are most  
effective when initiated before widespread tau accumulation and irreversible neurodegeneration.  
Because AD begins years before symptoms develop, identifying individuals most likely to develop  
rapid tau accumulation remains a major challenge. During this preclinical stage, amyloid may  
already be elevated while tau pathology, which is more closely linked to cognitive decline, remains  
subtle, spatially heterogeneous, and difficult to quantify.  
Tau PET allows researchers to visualize and quantify tau pathology in living people, but current  
analyses focus primarily on measuring the amount and spatial distribution of existing tau pathology.  
Dynamic tau PET also measures how the tracer is delivered through brain tissue before binding to  
tau proteins, providing information related to regional cerebral perfusion. Although this information  
is typically overlooked, it may reveal biological features of the brain that influence which regions are  
most vulnerable to future tau accumulation.  
This project will use advanced mathematical modeling of dynamic tau PET scans from cognitively  
unimpaired older adults from the Harvard Aging Brain Study to identify perfusion-related brain  
phenotypes and networks, determine how they relate to the spatial distribution of early tau  
pathology, and test whether they improve prediction of where and how quickly tau accumulates  
beyond established AD biomarkers (e.g., amyloid PET and plasma biomarkers). By integrating  
molecular imaging with measures of brain perfusion, this work aims to improve our understanding  
of the earliest stages of AD and establish a new framework for identifying individuals and brain  
regions most vulnerable to tau accumulation. Ultimately, these findings could improve participant  
selection for prevention trials and motivate future studies using dynamic tau PET or combining tau  
PET with MRI-based measures of cerebral perfusion, cerebrovascular function, vascular risk, blood  
biomarkers, and cognition.



 

 

 





 

 

- ## Fellowships
    
     [Current Exchange Fellows](/fellowships/current-exchange-fellows) [Exchange Fellows](/fellowships/exchange-fellows)
- ## Fellowship Year
    
     [2025-2026](/fellowship-year/2025-2026)