Abstract
Cerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage (ICH) in elderly individuals and it is the result of the cerebrovascular deposition of beta-amyloid (Aβ) protein. CAA is frequently found in patients with Alzheimer's disease (AD), although it has an independent contribution to the cognitive deterioration associated with age. Specific apolipoproteins (Apo) have been associated with Aβ fibrillization and clearance from the brain. In this regard, in the present study, we analyzed the brain levels of ApoE, ApoA-I, and ApoJ/clusterin in autopsy brains from 20 post-mortem cases with CAA type I, CAA type II, with parenchymal Aβ deposits or without Aβ deposits. Our objective was to find a possible differential pattern of apolipoproteins distribution in the brain depending on the CAA pathological presentation. The protein expression levels were adjusted by the APOE genotype of the patients included in the study. We found that ApoE and ApoJ were abundantly present in meningeal, cortical, and capillary vessels of the brains with vascular Aβ accumulation. ApoE and ApoJ also deposited extracellularly in the parenchyma, especially in cases presenting Aβ diffuse and neuritic parenchymal deposits. In contrast, ApoA-I staining was only relevant in capillary walls in CAA type I cases. On the other hand, ICH was the principal cause of death among CAA patients in our cohort. We found that CAA patients with ICH more commonly had APOEε2 compared with CAA patients without ICH. In addition, patients who suffered an ICH presented higher vascular ApoE levels in brain. However, higher ApoE presence in cortical arteries was the only independent predictor of suffering an ICH in our cohort after adjusting by age and APOE genotype. In conclusion, while ApoE and ApoJ appear to be involved in both vascular and parenchymal Aβ pathology, ApoA-I seems to be mainly associated with CAA, especially in CAA type I pathology. We consider that our study helps to molecularly characterize the distribution subtypes of Aβ deposition within the brain.
Highlights
Cerebral beta-amyloidosis is defined as the anomalous deposition of β-amyloid (Aβ) protein in the brain
We examined whether the immunopositivity of apolipoprotein E (ApoE), apolipoprotein J (ApoJ), and apolipoprotein A-I (ApoA-I) in brain vessels was associated with vascular Aβ deposition and symptomatic intracerebral hemorrhages (ICH) appearance in patients affected by Cerebral Amyloid Angiopathy (CAA)
ApoE, ApoJ, and ApoA-I cerebral levels and localization were analyzed in brains from the four different groups of patients categorized according to the parenchymal and vascular Aß deposition determined by immunostaining (Figure 1)
Summary
Cerebral beta-amyloidosis is defined as the anomalous deposition of β-amyloid (Aβ) protein in the brain. In the most common form of Cerebral Amyloid Angiopathy (CAA), insoluble Aβ accumulates in the wall of the cortical and meningeal vessels, replacing the smooth muscle cells, and inducing vascular degeneration. In this regard, CAA can be neuropathologically classified as CAA type I, which is characterized by Aβ deposition in cerebral capillaries, or CAA type II, where cerebral capillaries are not involved [1]. AD is the most frequent neurodegenerative disease, morphologically characterized by the presence of hyperphosphorylated tau protein in the cytoplasm of neurons and extracellular Aβ deposits forming parenchymal plaques. The combination of factors that determine whether Aβ accumulation occurs in parenchyma, developing into AD, or exclusively in blood brain vessels, triggering CAA-associated ICHs, still needs to be elucidated. Evidence for that is the presence of vascular amyloid and the occurrence of cerebral microhemorrhages and vasogenic edema when parenchymal Aβ is mobilized by active or passive immunization in AD [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
