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The article published in Brain Pathology discusses the decreased levels of claudin-5 in the microvasculature of patients with cerebral amyloid angiopathy (CAA) associated with intracerebral hemorrhage (ICH). The study aimed to investigate the role of claudin-5 in CAA-related ICH and found that claudin-5 expression was lower in CAA-ICH cases compared to CAA non-hemorrhagic cases and controls. The findings suggest that decreased claudin-5 levels may be linked to an increased risk of vessel rupture in patients with CAA. Further research is needed to explore the molecular mechanisms underlying this association. [Extracted from the article]

Objective: Elevated levels of anti‐amyloid‐β (anti‐Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy‐related inflammation (CAA‐RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA‐RI. Methods: We replicated the immunoassay to detect CSF anti‐Aβ autoantibodies using CSF from CAA‐RI patients and non‐CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA‐RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA‐RI. Results: The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (rsp = 0.51, p = 0.02). Assay levels were not elevated in CAA‐RI patients (n = 6) compared to non‐CAA controls (n = 20; p = 0.64). Literature review indicated only occasional presence of B‐lymphocytes and plasma cells (i.e., antibody‐producing cells), alongside the abundant presence of activated microglial cells, T‐cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production. Interpretation: We were unable to reproduce the reported elevation of anti‐Aβ autoantibody concentration in CSF of CAA‐RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA‐RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti‐Aβ autoantibodies as a diagnostic biomarker for CAA‐RI. [ABSTRACT FROM AUTHOR]

Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and linked to immunotherapy-related side-effects in Alzheimer’s disease (AD). Given ongoing efforts to develop AD immunotherapy, accurate estimates of CAA prevalence are important. CAA can be diagnosed neuropathologically or during life using MRI markers including strictly lobar microbleeds. In this meta-analysis of 170 studies including over 73,000 subjects, we show that in patients with AD, CAA prevalence based on pathology (48%) is twice that based on presence of strictly lobar cerebral microbleeds (22%); in the general population this difference is three-fold (23% vs 7%). Both methods yield similar estimated prevalences of CAA in cognitively normal elderly (5% to 7%), in patients with intracerebral hemorrhage (19% to 24%), and in patients with lobar intracerebral hemorrhage (50% to 57%). However, we observed large heterogeneity among neuropathology and MRI protocols, which calls for standardized assessment and reporting of CAA. [ABSTRACT FROM AUTHOR]

The following sentence in the Results section (under the paragraph heading "CSF A Levels in Patients with AD Compared to Patients with sCAA and Controls: Validation Group"): I "The combination of CSF A 40 and A 43 in combination with either A 38 or A 42 both yielded the highest AUC (0.96, 95% CI = 0.92-1.0)" i should be changed to: I "The combination of CSF B A 42 b and CSF A 43 with either A 38 or B A 40 b yielded the highest AUCs (0.96, 95% CI = B 0.91 b -1.0, and 0.96, 95% CI = 0.92-1.0, respectively)." i The following sentence in first paragraph of the Discussion: I "The combination of A 40, A 43, and either A 38 or A 42 yielded an AUC of 0.96 to discriminate sCAA from AD patients" i should be changed to: I "The combination of B A 42 b , A 43, and either A 38 or B A 40 b yielded an AUC of 0.96 to discriminate sCAA from AD patients." Correction: Decreased Cerebrospinal Fluid Amyloid 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy i The following sentence in the fifth paragraph of the Discussion: " I However, we show that the combination of A 40, A 43, and either A 38 or A 42 yielded an AUC of 0.96 to discriminate sCAA from AD" i should be changed to: I "However, we show that the combination of B A 42 b , A 43, and either A 38 or B A 40 b yielded an AUC of 0.96 to discriminate sCAA from AD." i We regret and sincerely apologize for the error. [Extracted from the article]

Background and Purpose: Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH)., Methods: We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models., Results: We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts., Conclusion: The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.

Reported prevalence estimates of sporadic cerebral amyloid angiopathy (CAA) vary widely. CAA is associated with cognitive dysfunction and intracerebral hemorrhage, and linked to immunotherapy-related side-effects in Alzheimer's disease (AD). Given ongoing efforts to develop AD immunotherapy, accurate estimates of CAA prevalence are important. CAA can be diagnosed neuropathologically or during life using MRI markers including strictly lobar microbleeds. In this meta-analysis of 170 studies including over 73,000 subjects, we show that in patients with AD, CAA prevalence based on pathology (48%) is twice that based on presence of strictly lobar cerebral microbleeds (22%); in the general population this difference is three-fold (23% vs 7%). Both methods yield similar estimated prevalences of CAA in cognitively normal elderly (5% to 7%), in patients with intracerebral hemorrhage (19% to 24%), and in patients with lobar intracerebral hemorrhage (50% to 57%). However, we observed large heterogeneity among neuropathology and MRI protocols, which calls for standardized assessment and reporting of CAA., (© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)