Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Abstract

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer’s disease (AD) pathogenesis through amyloid-β (Aβ) deposition, which may cause the development and progression of dementia. Despite extensive studies to explore drugs targeting Aβ, clinical benefits have not been reported in large clinical trials in AD patients or presymptomatic individuals at a risk for AD. However, recent studies on CAA and AD have provided novel insights regarding CAA- and AD-related pathogenesis. This work has revealed potential therapeutic targets, including Aβ drainage pathways, Aβ aggregation, oxidative stress, and neuroinflammation. The functional significance and therapeutic potential of bioactive molecules such as cilostazol and taxifolin have also become increasingly evident. Furthermore, recent epidemiological studies have demonstrated that serum levels of a soluble form of triggering receptor expressed on myeloid cells 2 (TREM2) may have clinical significance as a potential novel predictive biomarker for dementia incidence. This review summarizes recent advances in CAA and AD research with a focus on discussing future research directions regarding novel therapeutic approaches and predictive biomarkers for CAA and AD.

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis

“…The idea to use CSF parameters to diagnose CAA rests on the assumption that assessing the pathological agent itself might improve diagnostic accuracy and could help to make the diagnosis earlier and maybe facilitating opportunities to prevent the progression of the disease in the future ( Tanaka et al, 2020 ). Nevertheless, this study and the quantitative meta-analysis underlines that the differentiation between CAA and AD using CSF parameters analyzed in this study proves to be difficult.…”

AIEgen‐enhanced protein imaging: Probe design and sensing mechanisms

“…Amyloid, serum albumin, and alkaline phosphatase (ALP) are some examples of such proteins. [ 32–34 ] Furthermore, in some specific cancer types or tumors, overexpressed proteins such as integrins and cathepsins could be considered as their unique characteristic. [ 35,36 ] Accordingly, different strategies could be utilized for cell monitoring based on their protein moieties.…”

“…The transformation of soluble monomeric Aβ to filamentous aggregates is related to various diseases, from neurogenerative disorders such as Alzheimer's disease to diabetes. [32,[67][68][69] Zhang et al [70] have constructed a bioprobe (AIE-GNP) by combining a silole-based AIEgen (DES) and fluorescent glycoprobes (DK1 or DK2) for Aβ detection. Due to the FRET between the two molecules, this assembly resulted in a strong fluorescence emission of glycolprobes.…”

Research Progress on Mechanism of Neuroprotective Roles of Apelin-13 in Prevention and Treatment of Alzheimer’s Disease

“…Further development of CAA leads to BBB damage, micro-ischemia and cerebral infarction [ 129 , 130 ]. The activities of β- and γ-secreting enzymes are increased under hypoxia and ischemia, resulting to an increase in the production of APP [ 131 ]. At the same time, the damage of BBB blocked the clearance of neurotoxic substances such as APP and Aβ, which further led to the formation of amyloid plaques, massive loss of neurons as well as brain atrophy, and hence exacerbate the performance of AD [ 132 ].…”