title: ³H-deprenyl and ³H-PIB autoradiography show different laminar distributions of astroglia and fibrillar β-amyloid in Alzheimer brain.
abstract: BACKGROUND
  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 aid the development of specific biomarkers to accurately chart disease progression.
  
  
  RESULTS
  In vitro binding assays demonstrated increased [³H]-PIB (fibrillar Aβ) 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 (α4β2 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 [¹²⁵I]-α-bungarotoxin (α7 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 Aβ, 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 α7 nAChR expressing GFAP+ astrocytes both in the vicinity and surrounding Aβ neuritic plaques in the FC and HIP. Although fewer Aβ plaques were observed in the HIP, some hippocampal GFAP+ astrocytes contained Aβ-positive (6 F/3D) granules within their somata.
  
  
  CONCLUSIONS
  Astrocytosis shows a distinct regional pattern in AD brain compared to fibrillar Aβ, suggesting that different types of astrocytes may be associated with the pathophysiological processes in AD.
authors.affiliation: Alzheimer Neurobiology Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Novum Floor-5, Stockholm S-14186, Sweden.
authors.forename: Amelia
authors.initials: A
authors.lastname: Marutle
authors.forename: Per-Göran
authors.initials: PG
authors.lastname: Gillberg
authors.forename: Assar
authors.initials: A
authors.lastname: Bergfors
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Yu
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Ni
authors.forename: Inger
authors.initials: I
authors.lastname: Nennesmo
authors.forename: Larysa
authors.initials: L
authors.lastname: Voytenko
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001253:Astrocytes / Q000000981:diagnostic imaging* / Q000473:pathology*; D001345:Autoradiography; D052160:Benzothiazoles; D002038:Bungarotoxins / Q000494:pharmacology; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D007553:Isotope Labeling; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology; D011877:Radionuclide Imaging; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline; D009435:Synaptic Transmission / Q000502:physiology; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002038:Bungarotoxins; D007546:Isoquinolines; D011978:Receptors, Nicotinic; D013844:Thiazoles; C403531:nicotinic receptor alpha4beta2; D012642:Selegiline; D009538:Nicotine; C037850:PK 11195