INS NYC 2024 Program

Poster	Poster Session 06 Program Schedule 02/15/2024 04:00 pm - 05:15 pm Room: Majestic Complex (Posters 61-120) Poster Session 06: Aging \| MCI \| Neurodegenerative Disease - PART 2 Final Abstract #92 Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults Rowan Saloner, University of California, San Francisco, San Francisco, United States Lawren VandeVrede, University of California, San Francisco, San Francisco, United States Breton Asken, University of Florida, Gainesville, United States Emily Paolillo, University of California, San Francisco, San Francisco, United States Eva Gontrum, University of California, San Francisco, San Francisco, United States Amy Wolf, University of California, San Francisco, San Francisco, United States Argentina Lario-Lago, University of California, San Francisco, San Francisco, United States Marta Milà-Alomà, University of California, San Francisco, San Francisco, United States Gallen Triana-Baltzer, Janssen Research & Development, San Diego, United States Hartmuth Kolb, Janssen Research & Development, San Diego, United States Dena Dubal, University of California, San Francisco, San Francisco, United States Gil Rabinovici, University of California, San Francisco, San Francisco, United States Bruce Miller, University of California, San Francisco, San Francisco, United States Adam Boxer, University of California, San Francisco, San Francisco, United States Kaitlin Casaletto, University of California, San Francisco, San Francisco, United States Joel Kramer, University of California, San Francisco, San Francisco, United States Category: Dementia (Alzheimer's Disease) Keyword 1: dementia - Alzheimer's disease Keyword 2: hippocampus Keyword 3: memory disorders Objective: Plasma phosphorylated tau-217 (P-tau217) is a promising non-invasive and cost-effective fluid biomarker for preclinical diagnosis and prognosis of Alzheimer’s disease (AD). Accumulating evidence indicates disproportionate tau burden and tau-related clinical progression in females. However, it is unclear whether sex impacts plasma phosphorylated tau-217 (P-tau217) prediction of domain-specific cognitive decline and regional brain atrophy in cognitively unimpaired (CU) adults. Participants and Methods: Participants included 85 CU (44 males, 41 females) and 78 patients with mild cognitive impairment (MCI; 37 males, 41 females) enrolled in longitudinal studies at the UCSF Memory and Aging Center. Blood samples were collected at baseline and plasma was assayed for P-tau217 (Janssen), glial fibrillary acidic protein (GFAP; Quanterix Simoa), and neurofilament light (NfL; Quanterix Simoa). CU and MCI participants completed longitudinal cognitive testing (average follow-up=5.6 years), and CU also completed longitudinal brain MRI (average follow-up=4.8 years). A combined subset of CU (n=53) and MCI (n=35) participants underwent Aβ-PET imaging. In CU, linear-mixed effects models examined sex differences in plasma biomarker prediction of longitudinal domain-specific cognitive decline and brain volume atrophy. Cognitive models were repeated in MCI. Secondary models examined whether sex altered thresholds at which plasma P-tau217 corresponded to early pathological levels of Aβ-PET burden (12 centiloids). Results: In CU females, baseline plasma P-tau217 predicted verbal memory (β=-0.29, p=.004) and medial temporal lobe trajectories (β=-0.18, p=.028) such that trajectories significantly declined once P-tau217 concentrations surpassed 0.053 pg/ml, a threshold that corresponded to early levels of cortical amyloid aggregation in secondary amyloid-PET analyses, irrespective of sex. CU males exhibited similar rates of cognitive decline and brain atrophy, but these trajectories were not dependent on plasma P-tau217 (ps>.05). Plasma GFAP and NfL exhibited similar female-specific prediction of medial temporal lobe atrophy in CU (ps<.028) . Plasma P-tau217 exhibited comparable prediction of cognitive decline across sex in MCI. Conclusions: This longitudinal study observed sex-specific associations between baseline plasma P-tau217 and cognitive and brain trajectories. Females were disproportionately vulnerable to the adverse effects of elevated plasma P-tau217 on verbal memory decline and medial temporal lobe atrophy at the CU stage, whereas males exhibited P-tau217-related cognitive decline at the MCI stage. Plasma P-tau217 may capture earlier AD-related cognitive and brain atrophy hallmarks in females compared to males, possibly reflective of increased susceptibility to AD pathophysiology.

Poster

02/15/2024
04:00 pm - 05:15 pm
Room: Majestic Complex (Posters 61-120)

Poster Session 06: Aging | MCI | Neurodegenerative Disease - PART 2

Final Abstract #92

Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults

Rowan Saloner, University of California, San Francisco, San Francisco, United States
Lawren VandeVrede, University of California, San Francisco, San Francisco, United States
Breton Asken, University of Florida, Gainesville, United States
Emily Paolillo, University of California, San Francisco, San Francisco, United States
Eva Gontrum, University of California, San Francisco, San Francisco, United States
Amy Wolf, University of California, San Francisco, San Francisco, United States
Argentina Lario-Lago, University of California, San Francisco, San Francisco, United States
Marta Milà-Alomà, University of California, San Francisco, San Francisco, United States
Gallen Triana-Baltzer, Janssen Research & Development, San Diego, United States
Hartmuth Kolb, Janssen Research & Development, San Diego, United States
Dena Dubal, University of California, San Francisco, San Francisco, United States
Gil Rabinovici, University of California, San Francisco, San Francisco, United States
Bruce Miller, University of California, San Francisco, San Francisco, United States
Adam Boxer, University of California, San Francisco, San Francisco, United States
Kaitlin Casaletto, University of California, San Francisco, San Francisco, United States
Joel Kramer, University of California, San Francisco, San Francisco, United States

Category: Dementia (Alzheimer's Disease)

Keyword 1: dementia - Alzheimer's disease
Keyword 2: hippocampus
Keyword 3: memory disorders

Objective:

Plasma phosphorylated tau-217 (P-tau217) is a promising non-invasive and cost-effective fluid biomarker for preclinical diagnosis and prognosis of Alzheimer’s disease (AD). Accumulating evidence indicates disproportionate tau burden and tau-related clinical progression in females. However, it is unclear whether sex impacts plasma phosphorylated tau-217 (P-tau217) prediction of domain-specific cognitive decline and regional brain atrophy in cognitively unimpaired (CU) adults.

Participants and Methods:

Participants included 85 CU (44 males, 41 females) and 78 patients with mild cognitive impairment (MCI; 37 males, 41 females) enrolled in longitudinal studies at the UCSF Memory and Aging Center. Blood samples were collected at baseline and plasma was assayed for P-tau217 (Janssen), glial fibrillary acidic protein (GFAP; Quanterix Simoa), and neurofilament light (NfL; Quanterix Simoa). CU and MCI participants completed longitudinal cognitive testing (average follow-up=5.6 years), and CU also completed longitudinal brain MRI (average follow-up=4.8 years). A combined subset of CU (n=53) and MCI (n=35) participants underwent Aβ-PET imaging. In CU, linear-mixed effects models examined sex differences in plasma biomarker prediction of longitudinal domain-specific cognitive decline and brain volume atrophy. Cognitive models were repeated in MCI. Secondary models examined whether sex altered thresholds at which plasma P-tau217 corresponded to early pathological levels of Aβ-PET burden (12 centiloids).

Results:

In CU females, baseline plasma P-tau217 predicted verbal memory (β=-0.29, p=.004) and medial temporal lobe trajectories (β=-0.18, p=.028) such that trajectories significantly declined once P-tau217 concentrations surpassed 0.053 pg/ml, a threshold that corresponded to early levels of cortical amyloid aggregation in secondary amyloid-PET analyses, irrespective of sex. CU males exhibited similar rates of cognitive decline and brain atrophy, but these trajectories were not dependent on plasma P-tau217 (ps>.05). Plasma GFAP and NfL exhibited similar female-specific prediction of medial temporal lobe atrophy in CU (ps<.028) . Plasma P-tau217 exhibited comparable prediction of cognitive decline across sex in MCI.

Conclusions:

This longitudinal study observed sex-specific associations between baseline plasma P-tau217 and cognitive and brain trajectories. Females were disproportionately vulnerable to the adverse effects of elevated plasma P-tau217 on verbal memory decline and medial temporal lobe atrophy at the CU stage, whereas males exhibited P-tau217-related cognitive decline at the MCI stage. Plasma P-tau217 may capture earlier AD-related cognitive and brain atrophy hallmarks in females compared to males, possibly reflective of increased susceptibility to AD pathophysiology.