Dataset Information

³H-deprenyl and ³H-PIB autoradiography show different laminar distributions of astroglia and fibrillar ?-amyloid in Alzheimer brain.

ABSTRACT: BACKGROUND: The pathological features in Alzheimer's disease (AD) brain include the accumulation and deposition of ?-amyloid (A?), activation of astrocytes and microglia and disruption of cholinergic neurotransmission. Since the topographical characteristics of these different pathological processes in AD brain and how these relate to each other is not clear, this motivated further exploration using binding studies in postmortem brain with molecular imaging tracers. This information could aid the development of specific biomarkers to accurately chart disease progression. RESULTS: In vitro binding assays demonstrated increased [³H]-PIB (fibrillar A?) and [³H]-PK11195 (activated microglia) binding in the frontal cortex (FC) and hippocampus (HIP), as well as increased binding of [³H]-L-deprenyl (activated astrocytes) in the HIP, but a decreased [³H]-nicotine (?4?2 nicotinic acetylcholine receptor (nAChR)) binding in the FC of AD cases compared to age-matched controls. Quantitative autoradiography binding studies were also performed to investigate the regional laminar distributions of [³H]-L-deprenyl, [³H]-PIB as well as [¹²?I]-?-bungarotoxin (?7 nAChRs) and [³H]-nicotine in hemisphere brain of a typical AD case. A clear lamination pattern was observed with high [³H]-PIB binding in all layers and [³H]-deprenyl in superficial layers of the FC. In contrast, [³H]-PIB showed low binding to fibrillar A?, but [³H]-deprenyl high binding to activated astrocytes throughout the HIP. The [³H]-PIB binding was also low and the [³H]-deprenyl binding high in all layers of the medial temporal gyrus and insular cortex in comparison to the frontal cortex. Low [³H]-nicotine binding was observed in all layers of the frontal cortex in comparison to layers in the medial temporal gyrus, insular cortex and hippocampus. Immunohistochemical detection in the AD case revealed abundant glial fibrillary acidic protein positive (GFAP+) reactive astrocytes and ?7 nAChR expressing GFAP+ astrocytes both in the vicinity and surrounding A? neuritic plaques in the FC and HIP. Although fewer A? plaques were observed in the HIP, some hippocampal GFAP+ astrocytes contained A?-positive (6 F/3D) granules within their somata. CONCLUSIONS: Astrocytosis shows a distinct regional pattern in AD brain compared to fibrillar A?, suggesting that different types of astrocytes may be associated with the pathophysiological processes in AD.

SUBMITTER: Marutle A

PROVIDER: S-EPMC3733895 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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³H-deprenyl and ³H-PIB autoradiography show different laminar distributions of astroglia and fibrillar β-amyloid in Alzheimer brain.

Marutle Amelia A Gillberg Per-Göran PG Bergfors Assar A Yu Wenfeng W Ni Ruiqing R Nennesmo Inger I Voytenko Larysa L Nordberg Agneta A

Journal of neuroinflammation 20130723

<h4>Background</h4>The pathological features in Alzheimer's disease (AD) brain include the accumulation and deposition of β-amyloid (Aβ), activation of astrocytes and microglia and disruption of cholinergic neurotransmission. Since the topographical characteristics of these different pathological processes in AD brain and how these relate to each other is not clear, this motivated further exploration using binding studies in postmortem brain with molecular imaging tracers. This information could ...[more]

PMID: 23880036

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Project description:BackgroundDown syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined.ObjectivesTo characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death. Design/MethodsWith the family's informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient's diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient's diagnosis or PET measurements.ResultsVisual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan.ConclusionsFlorbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease.

Dataset Information

³H-deprenyl and ³H-PIB autoradiography show different laminar distributions of astroglia and fibrillar ?-amyloid in Alzheimer brain.

Publications

³H-deprenyl and ³H-PIB autoradiography show different laminar distributions of astroglia and fibrillar β-amyloid in Alzheimer brain.

Similar Datasets

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