| Title: |
Relationships between plasma biomarkers, tau PET, FDG PET, and volumetric MRI in mild to moderate Alzheimer's disease patients |
| Authors: |
Matthews, Dawn C; Kinney, Jefferson W; Ritter, Aaron; Andrews, Randolph D; Strom, Erin N Toledano; Lukic, Ana S; Koenig, Lauren N; Revta, Carolyn; Fillit, Howard M; Zhong, Kate; Tousi, Babak; Leverenz, James B; Feldman, Howard H; Cummings, Jeffrey |
| Source: |
Alzheimer's & Dementia: Translational Research & Clinical Interventions, vol 10, iss 3 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2024 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Brain Disorders (rcdc); Neurodegenerative (rcdc); Dementia (rcdc); Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) (rcdc); Alzheimer's Disease (rcdc); Clinical Research (rcdc); Acquired Cognitive Impairment (rcdc); Aging (rcdc); Behavioral and Social Science (rcdc); Neurosciences (rcdc); Biomedical Imaging (rcdc); 4.1 Discovery and preclinical testing of markers and technologies (hrcs-rac); Neurological (hrcs-hc); A/T/N; Alzheimer's disease; FDG PET; flortaucipir; GFAP; Inflammation; NfL; plasma biomarkers; pTau-181; Tau PET; volumetric MRI; pTau‐181; 3209 Neurosciences (for-2020); 5202 Biological psychology (for-2020) |
| Description: |
INTRODUCTION: The "A/T/N" (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation ("I"). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt09h1d4s1; https://escholarship.org/uc/item/09h1d4s1; https://escholarship.org/content/qt09h1d4s1/qt09h1d4s1.pdf |
| DOI: |
10.1002/trc2.12490 |
| Availability: |
https://escholarship.org/uc/item/09h1d4s1; https://escholarship.org/content/qt09h1d4s1/qt09h1d4s1.pdf; https://doi.org/10.1002/trc2.12490 |
| Rights: |
CC-BY-NC-ND |
| Accession Number: |
edsbas.20CCCE09 |
| Database: |
BASE |