# Pathophysiology of vitamin B1 (thiamin) transport in Alzheimer's disease

> **NIH NIH R01** · SOUTHERN CALIFORNIA INST FOR RES/EDUC · 2020 · $330,943

## Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by Amyloid-β peptide (Aβ)-
containing plaques, neurofibrillary tangles and cognitive deficits. Mitochondrial dysfunction, oxidative stress
and diminished glucose metabolism are consistent features of AD. The pathophysiology of AD also includes
neuroinflammation, which is associated with an elevation of pro-inflammatory cytokines (e. g., TNF-α,
interleukin 1β).
Thiamine (vitamin B1; also referred to as the “energy vitamin”) is indispensable for normal oxidative
energy metabolism and ATP production in the mitochondria; it also plays an important role in reducing cellular
oxidative stress. Thus, deficiency of thiamine at the cellular level leads to impairment in oxidative energy
metabolism, a decrease in cellular ATP level, and to a propensity for oxidative stress; it also leads to
impairment in the function/structure of mitochondria.
Compelling evidence exists suggesting that thiamine homeostasis is altered in AD, and that deficiency of
the vitamin aggravates disease pathology. Brain cells obtain thiamin from the blood via a specialized carriermediated process that involves thiamine transporter-1 and -2 (products of the SLC19A2 and SLC19A3 genes,
respectively). Once internalized, thiamine is enzymatically converted to thiamin pyrophosphate (TPP) then
transported into mitochondria via another specialized carrier-mediated process that involves the mitochondrial
TPP transporter (MTPPT; product of the SLC25A19 gene). Recent preliminary studies from our laboratory
related to the parent R01 grant have shown that in two different human/animal tissues (the pancreas and the
intestine), prolonged exposure to pro-inflammatory cytokines leads to a significant inhibition in cellular thiamin
uptake as well as in transport of TPP into mitochondria. Given these data, we hypothesize here that thiamine
uptake by brain cells and subsequent transport of TPP into their mitochondria is similarly impacted by chronic
exposure to proinflammatory cytokines. This in turn leads to deficient/suboptimal cellular thiamine levels and
impairment in oxidative metabolism/ATP production, an increase in oxidative stress, and abnormality in
function/structure of mitochondria, which may contribute to the pathogenesis of AD. We will test this hypothesis
by accomplishing the following Specific Aims: 1) Investigate possible changes in level of expression of the
thiamine transporters SLC19A2, SLC19A3 and SLC25A19 in different regions of the brains of AD patients; 2)
Examine the effect of exposure of brain cells to pro-inflammatory cytokines on cellular thiamine uptake and
transport of TPP into their mitochondria and determine the molecular mechanisms involved; 3) Determine
changes in the level of expression and activity of THTR-1, THTR-2 and MTPPT in the brain of mouse models
of AD.

## Key facts

- **NIH application ID:** 10117711
- **Project number:** 3R01AA018071-12S1
- **Recipient organization:** SOUTHERN CALIFORNIA INST FOR RES/EDUC
- **Principal Investigator:** HAMID M SAID
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,943
- **Award type:** 3
- **Project period:** 2009-04-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117711

## Citation

> US National Institutes of Health, RePORTER application 10117711, Pathophysiology of vitamin B1 (thiamin) transport in Alzheimer's disease (3R01AA018071-12S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10117711. Licensed CC0.

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