Neuropathologic characteristics of familial Alzheimer disease : cotton wool plaques and neuronal migration

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Cotton wool plaque (CWP) is a pathologic alteration initially reported in association with variant Alzheimer disease (early onset of dementia and spastic paraparesis) caused by a deletion of exon 9 in the Presenilin 1 (PSEN1) gene. The aim of this study is to report the results of clinical and neuropathologic characteristics of eight individuals affected with early onset of Alzheimer disease (EOAD) and 'cotton wool plaques (CWPs)' in association with mutations L166P, G217D, V261F, V261I, P264L and A431E in the Presenilin 1 (PSEN1) gene. In order to appraise the clinical characteristics of EOAD-CWPs, we analyzed several symptoms that include spastic paraparesis. In addition, the frequency of CWPs and neuritic plaques (NPs) was assessed using the semi quantification of the CERAD methodology in the multiple anatomical regions such as cerebral cortex, subcortical nucleus, cerebellum and brainstem. Each section was stained using hematoxylin and eosin, Bielschowsky and/or Bodian methods as w … More ell as immunolabeled using antibodies raised against Aβ, tau and α-synuclein. In addition, neuronal migration abnormalities were analyzed in the cerebral white matter. All cases were characterized clinically by early onset of dementia, however spastic paraparesis was only found in cases with L166P and V261F mutation. Neuropathologically, numerous CWPs were seen in the cerebral cortex, striatum and amygdala. The frequency of CWPs was significantly higher than that of NPs in five mutations (L166P, G217D, V261F, V261I, A431E). In some instances, abnormal neurons were seen in the cerebral white matter. Besides dementia, clinical presentation is heterogeneous and spastic paraparesis is not obligatory symptoms in EOAD-CWPs. The distribution of CWPs differs from that of NPs in which it extends to the striatum and midbrain. If CWPs are present, they are generally severest modality of plaques in the cerebrum. Our results may provide the information of clinical and neuropathologic heterogeneities of EOAD-CWPs. (297 words) Less