HAI Book 2025 - Flipbook - Page 272
Grothe, Michel
Plasma extracellular vesicle TDP-43 and hippocampal volume as
complementary biomarkers for LATE-NC and hippocampal sclerosis: a
pathologic validation study
Michel Grothe1, Linda Zhang1, Jesús Silva-Rodriguez1, Francisco López-González1, Minerva
Martinez-Castillo1, Selçuk Özdemir2, Alberto Rábano1, Pascual Sánchez-Juan1, Anja
Schneider2
1
Reina Sofia Alzheimer Center, CIEN Foundation, ISCIII, Madrid, ES
German Center for Neurodegenerative Diseases (DZNE), Bonn, DE
2
Background: Plasma extracellular vesicle TDP-43 (EV-TDP-43) has recently been proposed as a molecular
biomarker of TDP-43 pathology in frontotemporal dementia. We assessed the ability of EV-TDP-43 to detect
limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) in an autopsy cohort
of predominantly AD-type dementia patients. For comparison, we studied hippocampal volume (HV) on MRI as a
previously proposed imaging biomarker for LATE-NC and associated hippocampal sclerosis (HS).
Methods: We studied 74 autopsied dementia patients who had ante-mortem blood samples and quality-controlled
3T-MRI available. EV-TDP-43 was measured using size exclusion chromatography and SIMOA as described
recently. HV was derived from structural MRI using automated volumetry implemented in SPM12/CAT12.
Neuropathological examination included assessment of AD neuropathologic change (ADNC), LATE-NC, and
presence of HS.
Results: EV-TDP-43 levels were significantly higher (p=0.005) and HV (p=0.017) was significantly lower in LATENC(+)(n=50) compared to LATE-NC(-)(n=24), although group separation in ROC analysis was relatively weak (both
AUC=0.67). LATE-NC stage was weakly associated with EV-TDP-43 (rs=0.25; p=0.04) and more strongly with HV
(rs=-0.41; p
