Clearance of interstitial fluid (ISF) and CSF (CLIC) group‐part of Vascular Professional Interest Area (PIA), updates in 2022‐2023. Cerebrovascular disease and the failure of elimination of Amyloid‐β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy

Abstract

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age‐related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid‐related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA‐related inflammation (CAA‐ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.

Aggregation of gold nanoclusters in amyloid fibers: a luminescence assay for amyloid fibrillation detection and inhibitor screening

“…The related studies indicate that the detection of amyloid fibrils commonly occurs in cerebrospinal fluid or human plasma. 42–45 It appears that the detection of lysozyme fibrosis can exclude interferences from metal ions, amylase, bovine serum albumin (BSA), human serum albumin, alkaline phosphatase, trypsin, DNA and RNA, as described in the literature. 28,46 On the basis of the response of the Au NCs to the fibers, we applied Au NCs to the detection of lysozyme amyloid fibrillation.…”

Clinical considerations in early-onset cerebral amyloid angiopathy

“… 297 The effectiveness of these systems is thought to be influenced by age and APOE genotype and might be additionally challenged by certain protein structures particularly prone to vascular aggregation. 297 , 298 Examples include: mutations associated with PrP-CAA, which all result in ‘anchorless’ PrP 297 ; ITM2B mutations in FBD and FDD, which both produce elongated forms of BRI2 protein of identical length; and APP missense mutations associated with severe CAA, most of which fall within a narrow region of the amyloid-β coding domain, between codons 692 and 694. 22 Monogenic forms of CAA might also allow the identification of elusive early disease biomarkers, particularly in pre-symptomatic mutation carriers, as has been the case in D-CAA.…”

Identifying diagnostic and prognostic factors in cerebral amyloid angiopathy‐related inflammation: A systematic analysis of published and seven new cases

“…Indeed, the proposed pathogenesis is an anti-Aβ autoantibody-mediated autoimmune inflammation that involves microglia/macrophages, CD4 + lymphocytes and (in a proportion of cases) MNGCs, forming vascular/ perivascular infiltration of CAA-affected meningeal/cortical vessels [81]. From the diagnostic perspective, asymmetric confluent WMH is proposed to represent vasogenic oedema developing secondary to increased vascular permeability and impaired perivascular/ intravascular drainage mechanisms [82][83][84]. This is thought to be a remote and likely secondary [82] consequence of overlying cortical/ meningeal vascular inflammation without specific/diagnostic histopathological features.…”