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Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases

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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 Aβ42 was deposited more predominantly than Aβ40 in three cases. However, in case 2, approximately twice as much Aβ40 as Aβ42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. α-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Aβ component of AD amyloid (NAC), a central fragment of α-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 Aβ40 and Aβ42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Aβ 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 α-synuclein and NAC deposition.

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Acknowledgments

We thank Dr. K. Tsuchiya for review of the manuscript and comments, Mr. M. Kobashi and Ms. M. Onbe for excellent technical assistance, and Ms. S. Murakami for help in collecting clinical information. This work was supported by a research grant from the Zikei Institute of Psychiatry and a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (15591227).

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Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

    Osamu Yokota, Seishi Terada, Hideki Ishizu, Hiroshi Ujike, Takeshi Ishihara, Hanae Nakashima & Shigetoshi Kuroda

  2. Department of Laboratory Medicine, Zikei Institute of Psychiatry, 100-2 Urayasuhon-cho, Okayama 702-8508, Japan

    Hideki Ishizu & Masuyuki Namba

  3. Department of Neurology, National Okayama Medical Center, 1711-1 Tamasu, Okayama 701-1192, Japan

    Yasuaki Hayashi

  4. Okayama Prefectural Hospital, 3-16 Shikatahon-machi, Okayama 700-0915, Japan

    Tetsuya Nishinaka

  5. Clinical Research Institute and Department of Neurology, National Minami-Okayama Hospital, 4066 Hayashima-cho, Tsukubo-gun, Okayama 701-0304, Japan

    Reiko Namba

  6. Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan

    Kenji Uéda

  7. Institut de Pharmacologie Moléculaire et Cellulaire, UMR6097, Centre National de la Recherche Scientifique, Univerisité de Nice-Sophia Antipolis, 06560, Valbonne, France

    Frédéric Checler

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  1. Osamu Yokota
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  2. Seishi Terada
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  13. Shigetoshi Kuroda
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Correspondence to Osamu Yokota.

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Yokota, O., Terada, S., Ishizu, H. et al. Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases. Acta Neuropathol 106, 348–356 (2003). https://doi.org/10.1007/s00401-003-0737-7

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  • DOI: https://doi.org/10.1007/s00401-003-0737-7

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