Cerebrospinal Fluid Biomarkers and Amyloid-β Elimination from the Brain in Cerebral Amyloid Angiopathy-Related Inflammation

Article type: Research Article

Authors: Sakai, Kenji^{a; b; *} | Noguchi-Shinohara, Moeko^{b; c} | Tanaka, Hidetomo^d | Ikeda, Tokuhei^b | Hamaguchi, Tsuyoshi^{b; e} | Kakita, Akiyoshi^d | Yamada, Masahito^{b; f} | Ono, Kenjiro^b

Affiliations: [a] Department of Neurology, Joetsu General Hospital, Joetsu, Japan | [b] Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan | [c] Department of Preemptive Medicine for Dementia, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan | [d] Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan | [e] Department of Neurology, Kanazawa Medical University, Uchinada, Japan | [f] Department of Internal Medicine, Kudanzaka Hospital, Tokyo, Japan

Correspondence: [*] Correspondence to: Kenji Sakai, MD, PhD, Department of Neurology, Joetsu General Hospital 616 Daidofukuda, Joetsu 943-8507, Japan. Tel.: +81 25 524 3000; Fax: +81 25 524 3002; E-mail: [email protected].

Abstract: Background:Cerebrospinal fluid (CSF) biomarkers in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) have demonstrated inconsistent results. Objective:We investigated the relationship between CSF amyloid-β protein (Aβ) and vascular pathological findings to elucidate the mechanisms of Aβ elimination from the brain in CAA-ri. Methods:We examined Aβ40 and Aβ42 levels in CSF samples in 15 patients with CAA-ri and 15 patients with Alzheimer’s disease and cerebral amyloid angiopathy (AD-CAA) using ELISA as a cross-sectional study. Furthermore, we pathologically examined Aβ40 and Aβ42 depositions on the leptomeningeal blood vessels (arteries, arterioles, and veins) using brain biopsy samples from six patients with acute CAA-ri and brain tissues of two autopsied patients with CAA-ri. Results:The median Aβ40 and Aβ42 levels in the CSF showed no significant difference between pre-treatment CAA-ri (Aβ40, 6837 pg/ml; Aβ42, 324 pg/ml) and AD-CAA (Aβ40, 7669 pg/ml, p = 0.345; Aβ42, 355 pg/ml, p = 0.760). Aβ40 and Aβ42 levels in patients with post-treatment CAA-ri (Aβ40, 1770 pg/ml, p = 0.056; Aβ42, 167 pg/ml, p = 0.006) were lower than those in patients with pre-treatment CAA-ri. Regarding Aβ40 and Aβ42 positive arteries, acute CAA-ri cases showed a higher frequency of partially Aβ-deposited blood vessels than postmortem CAA-ri cases (Aβ40, 20.8% versus 3.9%, p = 0.0714; Aβ42, 27.4% versus 2.0%, p = 0.0714, respectively). Conclusion:Lower levels of CSF Aβ40 and Aβ42 could be biomarkers for the cessation of inflammation in CAA-ri reflecting the recovery of the intramural periarterial drainage pathway and vascular function.

Keywords: Amyloid-β protein-related angiitis, amyloid-related imaging abnormalities, biomarker, cerebral amyloid angiopathy-related inflammation, cerebrospinal fluid, diagnosis, elimination, pathology, vasculitis

DOI: 10.3233/JAD-220838

Journal: Journal of Alzheimer's Disease, vol. 91, no. 3, pp. 1173-1183, 2023