Brain ApoA-I, ApoJ and ApoE Immunodetection in Cerebral Amyloid Angiopathy

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.

NANOTHERAPY TO DELAY COGNITIVE IMPAIRMENT: USING COLLOIDAL NANOCARRIERS TO BLOCK AMYLOID-β-INDUCED DAMAGE IN BRAIN CELL MEMBRANES

“…Consistent with the above considerations concerning endothelial dysfunction in Alzheimer's disease, ApoA -I has very recently been reported by Camacho et al [75] to play a special role in cerebral amyloid angiopathy (CAA). CAA is observed in more than 90% of patients with Alzheimer's disease, although it additionally has an independent contribution to the cognitive deterioration associated with age.…”

“…CAA can be neuropathologically classified as CAA type I or type II, where type I is characterized by amyloid-β deposition in cerebral capillaries (versus type II where cerebral capillaries are not involved). The human data (from autopsy brains of 20 post-mortem cases), reported by Camacho et al, revealed that the ApoA-I immunohistochemical staining was localized strongly toward capillary walls with CAA (i.e., especially toward CAA type I pathology) [75]. Also, as alluded to above (see Abstract), the previously documented similarities in lipid composition among HDL (as well as native low-density lipoproteins (LDL) and modified LDL) and LCM/ND nanoemulsion particles can partially simulate or mimic the known heterogeneity (i.e., subpopulations or subspecies) of HDL particles (see [73] for a review).…”

Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways

“…Co-deposited proteins and apolipoproteins-Aβ that is deposited in neuritic plaques and vessels is accompanied by Aβ-associated proteins, including complement proteins, serum amyloid P component, α1-antichymotrypsin, glycosaminoglycans, matrix metalloproteinase 9 (MMP9) and various apolipoproteins, such as apolipoprotein E, apolipoprotein J (also known as clusterin) and apolipoprotein A-I [133][134][135][136][137][138][139][140][141][142][143][144][145] (Table 1). When, how and at what concentrations these associated proteins are co-deposited with Aβ remain to be determined, but some of these components can accelerate or inhibit the formation of Aβ fibrils [146][147][148][149][150] .…”

Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

“…We were particularly interested in studying the distribution of ApoJ in circulating lipoproteins because of its potential to participate in Aβ accumulation and clearance and modulate the balance between Aβ levels in brain vessels and parenchymal plaques [ 66 ]. In addition, ApoJ is co-deposited with fibrillary Aβ in both parenchymal plaques and vascular Aβ deposits [ 67 , 68 , 69 , 70 ]. Therefore, we first analyzed the levels of circulating total ApoJ levels, although no statistically significant differences among groups were obtained.…”