title: Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases.
abstract: We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. oyokota1@yahoo.co.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokota
authors.forename: Seishi
authors.initials: S
authors.lastname: Terada
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Masuyuki
authors.initials: M
authors.lastname: Namba
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishinaka
authors.forename: Reiko
authors.initials: R
authors.lastname: Namba
authors.forename: Hanae
authors.initials: H
authors.lastname: Nakashima
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
authors.forename: Frédéric
authors.initials: F
authors.lastname: Checler
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001344:Autopsy / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism*; D009460:Neurologic Examination; D011328:Prions / Q000378:metabolism; D013194:Staining and Labeling; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D011328:Prions; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins