Our Research Projects

The Mission

To advance the understanding of early changes in Alzheimer's disease (AD), frontotemporal degeneration (FTD), and Lewy body disease (LBD) through cerebrospinal fluid (CSF) analysis.

To develop and validate novel diagnostic and prognostic biomarkers for AD, FTD, and LBD through process engineering and machine based learning.

To use biomarkers to identify treatments promising in changing the course of AD, FTD, and LBD.

To advance the detection of cognitive decline and dementia in Mandarin speakers using culturally and linguistically appropriate tools.

CSF, MRI, and PET biomarkers of inflammation in aging and Alzheimer's disease

Inflammation has been identified as a key factor in the development and progression of Alzheimer's disease from genetic studies and autopsy studies, but large previous trials using anti-inflammatory drugs (NSAID, IVIg) have shown negative or mixed findings. One particular reason can be inflammation plays a bigger role in the development of Alzheimer's disease in some people than others. Our preliminary studies have shown that about half of the people with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease pathology have more changes in one inflammatory pathway (complement-mediated) than others. We are proposing to study this further by analyzing people with normal cognition as well as people with MCI/mild dementia due to Alzheimer's disease pathology through modern tools including cerebrospinal fluid (CSF) and blood inflammatory protein measurements, immune cell characterization, MRI scans with a new contrast that highlights macrophages, and PET scans with two chemicals that tag the resident immune cells of the brain.

Publications

Higher CSF sTNFR1-related proteins associated with better prognosis in very early Alzheimer's disease https://www.nature.com/articles/s41467-021-24220-7

CSF cytokines in aging, multiple sclerosis, and dementia https://www.frontiersin.org/articles/10.3389/fimmu.2019.00480/full

Non-beta-amyloid/tau cerebrospinal fluid markers inform staging and progression in Alzheimer’s disease https://alzres.biomedcentral.com/articles/10.1186/s13195-018-0426-3

Alzheimer's biomarkers and endothelial dysfunction in older Black and White adults

Epidemiologic studies show that, compared to non-Hispanic white Americans, African Americans are more likely to develop MCI and Alzheimer's disease, have different genetic risks of developing Alzheimer's, and experience different rates of cognitive decline. We hypothesize that endothelial dysfunction independently contributes to cognitive impairment in African Americans with Alzheimer's pathology, and that this dysfunction enhances the neurotoxicity of Alzheimer's-associated brain changes.

Publications

Interleukin-9 alterations linked to Alzheimer's disease in African Americans https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.25543

Race modifies the relationship between cognition and Alzheimer's disease cerebrospinal fluid biomarkers https://alzres.biomedcentral.com/articles/10.1186/s13195-017-0315-1

Knowledge and Attitudes in Alzheimer’s Disease in a Cohort of Older African Americans and Caucasians http://aja.sagepub.com/content/early/2015/12/04/1533317515619037.abstract

Pre-symptomatic CSF changes in individuals with disease-causing FTD mutations

DNA changes which lead to familial FTD (aka mutations) are present from birth, yet symptoms generally do not develop until the 4th or 5th decade of life. If we can better understand the brain changes in the pre-symptomatic phase, we can provide early detection of brain dysfunction before any symptom is obvious. We can also design future clinical trials to delay the onset of symptoms. Our approach involves recruiting healthy adult children (>18) of patients suffering from familial FTD to undergo blood, CSF, and MRI analysis.

Novel CSF biomarkers for Lewy body disease

There is still no reliable test to diagnose Lewy body disease (LBD). Dr. Hu's laboratory has been working since 2009 to identify new tests for related disorders, but LBD has always evaded our effort. Over the past few years, scientists have discovered small cargoes called "exosomes" that carry materials from one cell to another. Because our collaborators Drs. Virginia Lee and John Trojanowski at University of Pennsylvania showed that the main LBD protein - alpha-synuclein - can spread from cell to cell, we are now investigating if cargoes carrying alpha-synuclein spread the disease. This work is supported by the Patterson Family Foundation.

Overcoming stigma towards becoming dementia friendly

"Dementia friendly" movements have caught on around the world, but there is very little work on what constitutes dementia-inclusive or dementia-friendly. Dr. Hu has led a group of international stakeholders to ask this and other related questions, which culminated in the 2017 Salzburg Global Seminar on Innovations in Dementia Care and Dementia Friendly Communities. As an outcome of this, we produced a call to individuals, sectors, organizations, and nations to follow the core principles of respect, collaboration, empathy, and sustainability in developing Dementia Inclusive and Friendly Communities. Past and on-going work are sponsored by Dementia Spotlight Foundation, and we are now working towards Dementia Friendly Dekalb - the first of its kind in Georgia!

Publications:

William Hu: “There’s a lot of good work going on, but not enough credit is given to the people” https://www.salzburgglobal.org/news/latest-news/article/william-hu-theres-a-lot-of-good-work-going-on-but-not-enough-credit-is-given-to-the-people.html

Salzburg Statement on innovations in dementia care and dementia-friendly communities. https://www.salzburgglobal.org/news/latest-news/article/salzburg-global-calls-for-innovations-in-dementia-care-and-dementia-friendly-communities-on-world-al.html