Hippocampal degeneration is associated with GFAP levels in individuals with vascular dementia independently of amyloidosis

Abstract Background Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aß pathology and mediates tau‐pathology in preclinical AD. However, the association of GFAP levels with the markers associated with VD is poorly understood. Method We assessed 796 participants from a research cohort (TRIAD: 355) and a memory clinic cohort (BICWALZ: 441) that were divided into four groups according to their Aß (Aß+/Aß‐) and WMH status (WMH+/WMH‐). WMH values were corrected by intracranial volume, and cutoffs were determined based on the highest WMH value within 50% of the individuals with the lowest WMH rate in the CU Aß‐ group. Biomarker mean level differences between groups were estimated via Ancova Tukey’s test, and linear regressions accounting for age, sex, and cognitive status were used to estimate the association. Result For TRIAD, WMH+/Aß+ individuals exhibit higher levels of plasma GFAP when compared to all groups except WMH‐/Aß+, with no differences in NfL levels and hippocampal volume between groups (Fig. 1A). In BICWALZ, only hippocampal volume differs between groups with lower levels observed in both WMH‐/Aß‐ and WMH‐/Aß+ (Fig. 1B’’). The association of GFAP and NfL was observed in all groups (Fig. 2A, 2B’). On the other hand, hippocampal degeneration was associated with higher GFAP levels in individuals with abnormal WMH and absence of Aß burden in both cohorts (Fig. 3A: TRIAD: ß= ‐0.3036; p= 0.0195; Fig. 3B’: BICWALZ: ß= ‐0.1791; p= 0.0125). Conclusion Our findings suggest that astrocyte reactivity, as indicated by plasma GFAP levels, plays a significant role in the hippocampal atrophy observed in patients with vascular disease. These results suggest that therapies targeting astrocyte reactivity could potentially alleviate progressive cognitive deficits commonly found in patients with chronic vasculopathy.

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Journal
Alzheimer s & Dementia
Published
2024-12-01
DOI
https://doi.org/10.1002/alz.094078
Citations
1
Primary Topic
Alzheimer's disease research and treatments
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article
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0.33
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article

Hippocampal degeneration is associated with GFAP levels in individuals with vascular dementia independently of amyloidosis

Hyun Woong Roh, Dana Tudorascu, Tharick Ali Pascoal, Joseph Therriault et al.
1 citations
Alzheimer s & Dementia
Alzheimer's disease research and treatments
0.33
article

Hippocampal degeneration is associated with GFAP levels in individuals with vascular dementia independently of amyloidosis

Hyun Woong Roh, Dana Tudorascu, Tharick Ali Pascoal, Joseph Therriault, Nicholas James Ashton, Cynthia Felix, Guilherme Povala, Douglas Teixeira Leffa, Eduardo Rigon Zimmer, Chang Hyung Hong, Carolina Soares, Sang Joon Son, Guilherme Bauer‐Negrini, Nesrine Rahmouni, Pâmela C.L. Ferreira, Emma Patrice Ruppert, Andréa Lessa Benedet, Matheus Scarpatto Rodrigues, Thomas K. Karikari, Stijn Servaes, Bruna Bellaver, Sarah Abbas, Firoza Zubeida Lussier, Cécile Tissot, Hussein Zalzale, Henrik Zetterberg, Andréia Silva da Rocha, Francieli Rohden, Pedro Rosa‐Neto, Pampa Saha, Jenna Stevenson, Kaj Blennow, Vanessa Machado, Markley S. Oliveira
article en
1 citations

Abstract

Abstract Background Vascular cognitive impairment/dementia (VD) is the second most prevalent cause of dementia following Alzheimer's disease (AD). VD is characterized by the progression of white matter hyperintensity burden (WMH) and associated neurodegeneration. GFAP, a biomarker for reactive astrogliosis, is associated with Aß pathology and mediates tau‐pathology in preclinical AD. However, the association of GFAP levels with the markers associated with VD is poorly understood. Method We assessed 796 participants from a research cohort (TRIAD: 355) and a memory clinic cohort (BICWALZ: 441) that were divided into four groups according to their Aß (Aß+/Aß‐) and WMH status (WMH+/WMH‐). WMH values were corrected by intracranial volume, and cutoffs were determined based on the highest WMH value within 50% of the individuals with the lowest WMH rate in the CU Aß‐ group. Biomarker mean level differences between groups were estimated via Ancova Tukey’s test, and linear regressions accounting for age, sex, and cognitive status were used to estimate the association. Result For TRIAD, WMH+/Aß+ individuals exhibit higher levels of plasma GFAP when compared to all groups except WMH‐/Aß+, with no differences in NfL levels and hippocampal volume between groups (Fig. 1A). In BICWALZ, only hippocampal volume differs between groups with lower levels observed in both WMH‐/Aß‐ and WMH‐/Aß+ (Fig. 1B’’). The association of GFAP and NfL was observed in all groups (Fig. 2A, 2B’). On the other hand, hippocampal degeneration was associated with higher GFAP levels in individuals with abnormal WMH and absence of Aß burden in both cohorts (Fig. 3A: TRIAD: ß= ‐0.3036; p= 0.0195; Fig. 3B’: BICWALZ: ß= ‐0.1791; p= 0.0125). Conclusion Our findings suggest that astrocyte reactivity, as indicated by plasma GFAP levels, plays a significant role in the hippocampal atrophy observed in patients with vascular disease. These results suggest that therapies targeting astrocyte reactivity could potentially alleviate progressive cognitive deficits commonly found in patients with chronic vasculopathy.

Alzheimer s & DementiaVol. 20(S9)
Universidade Federal do Rio Grande do Sul (BR), University of Wisconsin–Madison (US), Lawrence Berkeley National Laboratory (US), University of Pittsburgh (US), McGill University Health Centre (CA), McGill University (CA), Ajou University (KR), University of Gothenburg (SE)
Good health and well-being
Openalex Percentile: Top 34%
Alzheimer's disease research and treatments
0.33
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