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0696 Two types of Abeta removal by glial cells
Journalo/Ihe
Ne ELSEVIER
o!ogical clences
Journal of the Neurological Sciences 238 (2005) $277-$378 www.elsevier, com/locate/jns
Poster Abstracts
9 November 2005 0696 Two Types of Abeta Removal by Glial Cells Akiyama, H 1, KolldO, H 1, Haga, C 1, Slffmollmra, y 1 0 b i , K 2, Oshillla, K 3, Tsuctffya, K 3. 2Tokyo Institute of Psychiatry, Tokyo,
Japan; 2Juntozdo University, Tokyo, Japan; 3Tokyo Metropolitan Ivlatsuzawa Hospital, Tokyo, Japan Baekg*ound: In vitro and ill vivo studies have shown that, following intake by glial cells, amyloid-beta protein (Abeta) loses the epitopes of N-termillal sequence by illtracellular processing. In this study, we investigated the change o f immunochemical profiles o f Abeta together with the phenotypes of glial cells that accumulate Abeta intracellularly. Method: Postmortem brain tissues from patients with Alzheimer's disease were fixed in 4% paraformaldehyde, cryo-cut into free-floating sections and double-illmmnostailled for combinations of N- and C-terminal sequences o f Abeta, Abeta and microglial markers, or Abeta and astrocyfic markers. Results: Accumulation of Abeta that lacks the N-terminal sequence was seen in both microglia and astrocytes. Phellotypes of these cells indicate that they are resting or modestly activated. Occurrence of such Abeta containing glial cells varied from patient to patient and from region to region in a given patient. Within senile plaques, highlyactivated microglia that contain N-terminally modified Abeta were seen. Postmortem human brains are often complicated with mild ischemia/hypoxia that do not cause infarction but activate microglia. In senile plaques associated with such mild insults, illtrallffcroglial Abeta that was negative for the N-terminal sequence increased and extracelhilar Abeta that was positive for the N-terminal sequence decreased. Conclusions: Abeta is taken up by resting microglia/astrocytes as well as by reactive microglia. The latter process seems to be phagocytosis o f once-deposited, insoluble Abeta aggregates. Deposition of Abeta in senile plaques may depend on the dynmnic balance between the addition of newly secreted Abeta and the removal by reactive microglia. 0697 Amnestie Mild Cognitive Itllpaixillent: Applicabilily of Research Criteria in a Memory Clinic and Defidls Beyond Amnesia
ZNizam's Institute of Medical Sciences, Hyderabad, India; 2University of Cambridge, Neurology Unit, Cambridge, United Kingdom Alladi S l, Nestor pj2, Arnold R 2, Mitchell Ja, Hodges J R ~.
Background: Mild Cognitive Impairment (MCI) as defined by Petersell's criteria is regarded as all amllestic state that represents prodromal Alzheimer's disease (AD). However, controversies exist regarding definition of amnesia in MC[ and involvement of other cognitive functions. We aimed to evaluate applicability o f Petersen's
criteria ill a memory clinic, to assess how different lllelilory tests defined MCI and to study other cognitive deficits ill MC[. Method: Of 166 referrals with mild memory complaints, 124 nondemented, non-depressed cases were recruited into the Cambridge MC[ study. MCI was diagnosed by verbal memory based Petersen's criteria and further broadened to include performance on visual memory tests. Cognitive deficits beyond memory were studied ill the cohort. Results: Sevellty-two subjects fulfilled Petersell's criteria and all additional 18 were categorised as MCI on including performance on visual memory tests. Of 90 MCI subjects, 55 had impairment on more than one memory test. The majority (164/90), were found to have other cognitive deficits: semantic memory (ii -- 24), attelltiollal-execative function (11 - 22), visuospatial (ii _ 5) and three or more cognitive domains (n -- 13), Multiple domain involvement was more frequent among patients with both verbal and visual memory impairment. Twelve had non-amnesric cognitive impairment. Conclusion: Ill tiffs large study, Petersell's criteria showed good applicability ill clinical practice. The actual llmllber categorized as MC[ varied depending upon the number of memory tests used and modality of memory tested. Cognitive deficits beyond episodic memory were demonstrated in majority of amnestic MCI subjects and the pattern of cognitive deficits resembled heterogeneity observed in early AD.
0698 Widening the spectrum of Alzheimar's disease: Evidence from a large dinieopathologieal series of typical and atypical cases
ZNizam's Institute of Medical Sciences, Hyderabad, India," 2UnDersity of Cambridge, Cambridge, United Kingdom
Alladi S x, Knibb j 2 Xuereb JH 2, Hodges J R 2.
Background: Alzheimer's disease (AD) is typically regarded as an amllestic sylldrome. However, scattered reports of lloll-amllestic presentations of AD exist. Prominent amnesia ill IIoli-AD dementias has also been described. Pathological verification of clinically typical and atypical AD is limited. In a large clinicopathological series, we determined pathology in typical AD presentations and also studied clinical presentations of classic AD pathology. Method: Of 166 consecutive cases studied ill the Cambridge Brain Bank, 47 had either a clinical diagnosis ill life or a pathological diagnosis of AD. Neuropsychological, imaging and lleuropathological data were reviewed. Clinically typical and atypical AD cases were identified and groups compared for initial cognitive profile, evolution, survival and pathology. Results: Of 19 clinically typical AD, 18 had pathologically confirmed AD and one frolltotemporal dementia pathology. Of 46 with AD pathology, 18 had clinically typical and 28 had atypical AD. Progressive aphasia was the most common atypical subtype (nonfluent aphasia 0a -- equals; 8), mixed (n -- 1), fluent (n - 2) and semantic dementia 0a -- 2)), followed by posterior cortical atrophy (PCA, n - 7),
Ne ELSEVIER
o!ogical clences
Journal of the Neurological Sciences 238 (2005) $277-$378 www.elsevier, com/locate/jns
Poster Abstracts
9 November 2005 0696 Two Types of Abeta Removal by Glial Cells Akiyama, H 1, KolldO, H 1, Haga, C 1, Slffmollmra, y 1 0 b i , K 2, Oshillla, K 3, Tsuctffya, K 3. 2Tokyo Institute of Psychiatry, Tokyo,
Japan; 2Juntozdo University, Tokyo, Japan; 3Tokyo Metropolitan Ivlatsuzawa Hospital, Tokyo, Japan Baekg*ound: In vitro and ill vivo studies have shown that, following intake by glial cells, amyloid-beta protein (Abeta) loses the epitopes of N-termillal sequence by illtracellular processing. In this study, we investigated the change o f immunochemical profiles o f Abeta together with the phenotypes of glial cells that accumulate Abeta intracellularly. Method: Postmortem brain tissues from patients with Alzheimer's disease were fixed in 4% paraformaldehyde, cryo-cut into free-floating sections and double-illmmnostailled for combinations of N- and C-terminal sequences o f Abeta, Abeta and microglial markers, or Abeta and astrocyfic markers. Results: Accumulation of Abeta that lacks the N-terminal sequence was seen in both microglia and astrocytes. Phellotypes of these cells indicate that they are resting or modestly activated. Occurrence of such Abeta containing glial cells varied from patient to patient and from region to region in a given patient. Within senile plaques, highlyactivated microglia that contain N-terminally modified Abeta were seen. Postmortem human brains are often complicated with mild ischemia/hypoxia that do not cause infarction but activate microglia. In senile plaques associated with such mild insults, illtrallffcroglial Abeta that was negative for the N-terminal sequence increased and extracelhilar Abeta that was positive for the N-terminal sequence decreased. Conclusions: Abeta is taken up by resting microglia/astrocytes as well as by reactive microglia. The latter process seems to be phagocytosis o f once-deposited, insoluble Abeta aggregates. Deposition of Abeta in senile plaques may depend on the dynmnic balance between the addition of newly secreted Abeta and the removal by reactive microglia. 0697 Amnestie Mild Cognitive Itllpaixillent: Applicabilily of Research Criteria in a Memory Clinic and Defidls Beyond Amnesia
ZNizam's Institute of Medical Sciences, Hyderabad, India; 2University of Cambridge, Neurology Unit, Cambridge, United Kingdom Alladi S l, Nestor pj2, Arnold R 2, Mitchell Ja, Hodges J R ~.
Background: Mild Cognitive Impairment (MCI) as defined by Petersell's criteria is regarded as all amllestic state that represents prodromal Alzheimer's disease (AD). However, controversies exist regarding definition of amnesia in MC[ and involvement of other cognitive functions. We aimed to evaluate applicability o f Petersen's
criteria ill a memory clinic, to assess how different lllelilory tests defined MCI and to study other cognitive deficits ill MC[. Method: Of 166 referrals with mild memory complaints, 124 nondemented, non-depressed cases were recruited into the Cambridge MC[ study. MCI was diagnosed by verbal memory based Petersen's criteria and further broadened to include performance on visual memory tests. Cognitive deficits beyond memory were studied ill the cohort. Results: Sevellty-two subjects fulfilled Petersell's criteria and all additional 18 were categorised as MCI on including performance on visual memory tests. Of 90 MCI subjects, 55 had impairment on more than one memory test. The majority (164/90), were found to have other cognitive deficits: semantic memory (ii -- 24), attelltiollal-execative function (11 - 22), visuospatial (ii _ 5) and three or more cognitive domains (n -- 13), Multiple domain involvement was more frequent among patients with both verbal and visual memory impairment. Twelve had non-amnesric cognitive impairment. Conclusion: Ill tiffs large study, Petersell's criteria showed good applicability ill clinical practice. The actual llmllber categorized as MC[ varied depending upon the number of memory tests used and modality of memory tested. Cognitive deficits beyond episodic memory were demonstrated in majority of amnestic MCI subjects and the pattern of cognitive deficits resembled heterogeneity observed in early AD.
0698 Widening the spectrum of Alzheimar's disease: Evidence from a large dinieopathologieal series of typical and atypical cases
ZNizam's Institute of Medical Sciences, Hyderabad, India," 2UnDersity of Cambridge, Cambridge, United Kingdom
Alladi S x, Knibb j 2 Xuereb JH 2, Hodges J R 2.
Background: Alzheimer's disease (AD) is typically regarded as an amllestic sylldrome. However, scattered reports of lloll-amllestic presentations of AD exist. Prominent amnesia ill IIoli-AD dementias has also been described. Pathological verification of clinically typical and atypical AD is limited. In a large clinicopathological series, we determined pathology in typical AD presentations and also studied clinical presentations of classic AD pathology. Method: Of 166 consecutive cases studied ill the Cambridge Brain Bank, 47 had either a clinical diagnosis ill life or a pathological diagnosis of AD. Neuropsychological, imaging and lleuropathological data were reviewed. Clinically typical and atypical AD cases were identified and groups compared for initial cognitive profile, evolution, survival and pathology. Results: Of 19 clinically typical AD, 18 had pathologically confirmed AD and one frolltotemporal dementia pathology. Of 46 with AD pathology, 18 had clinically typical and 28 had atypical AD. Progressive aphasia was the most common atypical subtype (nonfluent aphasia 0a -- equals; 8), mixed (n -- 1), fluent (n - 2) and semantic dementia 0a -- 2)), followed by posterior cortical atrophy (PCA, n - 7),