# The impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's disease

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $746,957

## Abstract

Project Summary/Abstract
All individuals with Parkinson’s disease (PD) are at risk for developing memory impairment and dementia,
markedly increasing loss of employment, caregiver stress, increased cost to health systems, patient
institutionalization, and decreased survival. There are no interventions available to prevent this devastating
consequence of disease, making both PD Dementia (PDD) and the closely related Dementia with Lewy Bodies
(DLB) a looming public health crisis. At autopsy, less than 40% of patients exhibit only Lewy body (LB) pathology,
whereas 60-80% exhibit mixed LB and Alzheimer’s disease (LB/AD) pathology. Conversely, very few PD patients
are thought to have AD co-pathology at clinical diagnosis. Unfortunately, we know little about when PD patients
develop AD co-pathology, which creates a barrier to the development of effective therapies: PD patients without
AD co-pathology would be ideal candidates for α-synuclein targeted therapies, whereas PD patients with AD co-
pathology likely would require combination therapy. Experiments proposed here take a significant step toward
overcoming this barrier by identifying early Tau pathology in living patients relative to their cognitive progression.
To perform these experiments, we will leverage the perfect co-registration of simultaneous PET/MRI to identify
subtlely emerging Tau pathology in the medial temporal lobe. We will also determine whether the inflammatory
amplifier Triggering Receptor Expressed on Myeloid Cells 2, or TREM2, is elevated in PD patients with Tau PET
evidence of AD co-pathology, as is suggested by our preliminary data. Finally, we will determine the impact of
AD co-pathology on cognitive progression and the onset of neuropsychiatric symptoms, such as psychosis. We
will leverage the combined participants of the Pacific Udall Center and the Stanford Alzheimer’s disease
Research Center, which provides a unique opportunity to study a well-characterized population of PD patients
who are followed longitudinally with clinical assessments, biospecimen collection, and, ultimately, autopsy. A
collaborative team of neuroscientists at Stanford University with training in Movement Disorders Neurology,
Nuclear Medicine, Neuroimmunology, Biostatistics and Pathology will carry out these aims. The proposed
studies are highly relevant to the mission of the National Plan to Address Alzheimer's Disease, which calls to
improve dementia diagnosis and accelerate the development of treatments for Alzheimer's disease and related
dementias, such as Parkinson’s disease dementia.

## Key facts

- **NIH application ID:** 10246979
- **Project number:** 5R01NS115114-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Katrin I. Andreasson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $746,957
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246979

## Citation

> US National Institutes of Health, RePORTER application 10246979, The impact of early Tau pathology on cognitive progression and neuropsychiatric symptoms in Parkinson's disease (5R01NS115114-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246979. Licensed CC0.

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