Platelet and Plasma Phosphatidylcholines as Biomarkers to Diagnose Cerebral Amyloid Angiopathy.
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ABSTRACT:
SUBMITTER: Foidl BM
PROVIDER: S-EPMC7303320 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Platelet and Plasma Phosphatidylcholines as Biomarkers to Diagnose Cerebral Amyloid Angiopathy.
Foidl Bettina M BM Oberacher Herbert H Marksteiner Josef J Humpel Christian C
Frontiers in neurology 20200612
Alzheimer's disease is a severe neurodegenerative brain disorder and characterized by deposition of extracellular toxic β-amyloid (42) plaques and the formation of intracellular tau neurofibrillary tangles. In addition, β-amyloid peptide deposits are found in the walls of small to medium blood vessels termed cerebral amyloid angiopathy (CAA). However, the pathogenesis of CAA appears to differ from that of senile plaques in several aspects. The aim of the present study was to analyze different li ...[more]
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Project description:BackgroundThere is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).ObjectiveTo determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA.MethodsWe performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.ResultsWe included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ38, Aβ40, Aβ42, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an "AD-like" profile.ConclusionCAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.
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Project description:BackgroundDecreased cerebrospinal fluid (CSF) amyloid-? 1-40 (A?40) and amyloid-? 1-42 (A?42) and increased total and phosphorylated tau (t-tau, p-tau) concentrations have been described in cerebral amyloid angiopathy (CAA).ObjectiveOur aim was to analyze these biomarkers in patients with CAA-related inflammation (CAA-I).MethodsWe prospectively recruited nine patients with acute phase CAA-I fulfilling Chung criteria. CSF was analyzed for t-tau, p-tau, A?42, and A?40. Data were compared to controls (n?=?14), patients with Alzheimer's disease (AD, n?=?42), CAA (n?=?10), and primary angiitis of the central nervous system (PACNS, n?=?3).ResultsFor the CAA-I group, statistically significant differences were: lower A?42 (p?=?0.00053) compared to the control group; lower t-tau (p?=?0.018), p-tau (p?< ?0.001), and A?40 (p?< ?0.001) compared to AD; lower A?42 (p?=?0.027) compared to CAA; lower A?42 (p?=?0.012) compared to PACNS. Nearly significantly lower A?40 (p?=?0.051) and higher t-tau (p?=?0.051) were seen in CAA-I compared to controls.ConclusionCSF biomarkers profile similar to that of CAA was observed in CAA-I (with even lower levels of A?42 compared to CAA). Based on our findings, high p-tau seems more specific for AD, whereas low A?42 differentiates CAA-I from CAA, PACNS, and controls, and low A?40 differentiates CAA-I from AD.
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Project description:Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy that is classically associated with lobar intracerebral or sulcal hemorrhage. Its prevalence is estimated at 30% in the seventh decade and 50% in the eighth and ninth decades. In this review, we summarize the risks linked to CAA with respect to the treatment and prevention of stroke.This review is based on pertinent publications retrieved by a selective search employing the terms "amyloid cerebral angiopathy," "stroke," "intra - cerebral bleeding," and "acute stroke therapy."Among patients given systemic lytic treatment for stroke, those who have microhemorrhages tend to have a higher risk of treatment-associated brain hemorrhage. In a meta-analysis, 70% of patients who sustained a hemorrhage after thrombolytic therapy were found to have CAA, compared to only 22% in a control population. Patients with cerebral hemorrhages have microhemorrhages more commonly than patients with transient ischemic attacks (TIA) or infarcts. This was observed among persons under treatment with vitamin K antagonists (odds ratio, 2.7) or platelet aggregation inhibitors (odds ratio, 1.7). Moreover, the apolipoprotein E2 allele is associated with a higher incidence of intracerebral hemorrhage (ICH) under oral anticoagulation. Strict treatment of arterial hypertension can lower the risk of ICH in persons with probable CAA by 77%. On the other hand, the use of statins after a lobar ICH increases the risk for a clinically manifest recurrent hemorrhage from 14% to 22%.In patients with CAA, arterial hypertension should be tightly controlled. On the other hand, caution should be exercised in prescribing oral anticoagulants or platelet aggregation inhibitors for patients with CAA, or statins for patients who have already sustained a lobar ICH.
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Project description:Amyloid-? (A?) is a peptide deposited in the brain parenchyma in Alzheimer's disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). A? pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA. None of these patients carried pathogenic mutations associated with early A? pathology development. In addition, we identified in the literature four patients with a history of neurosurgical intervention and subsequent development of CAA. These findings raise the possibility that A? pathology may be transmissible, as prion disease is, through neurosurgical procedures.
| S-EPMC5904220 | biostudies-literature
Project description:Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer's disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.
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Project description:Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood-brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood-brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage. HIGHLIGHTS: The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review. There is an inflammatory response to beta-amyloid that may contribute to brain injury and cognitive impairment. Immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA.
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| S-EPMC3282897 | biostudies-literature
Project description:Background and Purpose- Hematoma location within the cerebellum may help identify the dominant small vessel disease type (cerebral amyloid angiopathy [CAA] versus nonamyloid small vessel disease). However, it is unknown whether this holds true for cerebral microbleeds (CMBs) within the cerebellum. We tested the hypothesis that cerebellar CMBs restricted to the cortex and vermis (defined as superficial regions) are associated with clinically diagnosed and pathology-verified CAA. Methods- Three hundred and seven consecutive spontaneous intracerebral hemorrhage (ICH) patients with a baseline magnetic resonance imaging that included susceptibility-weighted imaging or angiography were enrolled. Using a topographical template, cerebellar CMB patterns were defined as strictly superficial versus deep (cerebellar gray nuclei and white matter) or mixed (both regions involved). Thirty-six ICH patients with cerebellar CMBs and neuropathology data available were evaluated for the presence of CAA. Results- One hundred and thirty-five (44%) ICH patients had CMBs in the cerebellum. In the patient group with cerebellar CMBs, 85 (63%) showed a superficial pattern, and 50 (37%) had a deep/mixed pattern. Strictly superficial cerebellar CMBs were independently associated with a supratentorial pattern of probable CAA-ICH according to the Boston criteria (odds ratio, 1.6; CI, 1.03-2.5) and deep/mixed cerebellar CMBs with a pattern of deep/mixed ICH (odds ratio, 1.8; CI, 1.2-2.7). Pathologically verified CAA was present in 23 of 24 (96%) patients with superficial cerebellar CMBs versus 3 of 12 (25%) patients with deep/mixed cerebellar CMBs ( P<0.001). Conclusions- In ICH patients, cerebellar CMBs are relatively common and often restricted to superficial regions. A strictly superficial distribution of cerebellar CMBs is associated with clinically diagnosed and pathologically verified CAA.
| S-EPMC6599711 | biostudies-literature
Project description:OBJECTIVE:To determine whether common genetic variants in UNC5C, a recently identified late-onset Alzheimer disease (LOAD) dementia susceptibility gene, are associated with AD susceptibility or AD-related clinical/pathologic phenotypes. METHODS:We used data from deceased individuals of European descent who participated in the Religious Orders Study or the Rush Memory and Aging Project (n = 1,288). We examined whether there were associations between single nucleotide polymorphisms (SNPs) within ±100 kb of the UNC5C gene and a diagnosis of AD dementia, global cognitive decline, a pathologic diagnosis of AD, ?-amyloid load, neuritic plaque count, diffuse plaque count, paired helical filament tau density, neurofibrillary tangle count, and cerebral amyloid angiopathy (CAA) score. We also evaluated the relation of the CAA-associated variant and dorsolateral prefrontal cortex (DLPFC) UNC5C RNA expression. Secondary analyses were performed to examine the interaction of the CAA-associated SNP and known genetic risk factors of CAA as well as the association of the SNP with other cerebrovascular pathologies. RESULTS:A set of UNC5C SNPs tagged by rs28660566T was associated with a higher CAA score (p = 2.3 × 10-6): each additional rs28660566T allele was associated with a 0.60 point higher CAA score, which is equivalent to approximately 75% of the higher CAA score associated with each allele of APOE ?4. rs28660566T was weakly associated with lower UNC5C expression in the human DLPFC (p = 0.036). Moreover, rs28660566T had a synergistic interaction with APOE ?4 on their association with higher CAA severity (p = 0.027) and was associated with more severe arteriolosclerosis (p = 0.0065). CONCLUSIONS:Targeted analysis of the UNC5C region uncovered a set of SNPs associated with CAA.
| S-EPMC5515600 | biostudies-literature