Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs. Tau immunopositive neurites may be present in CWPs. In addition, neurofibrillary tangles coexist with CWPs. Herein, we report the structure of Aβ and tau filaments isolated from brain tissue of individuals affected by DIAD caused by the PSEN1 V261I and A431E mutations, with the CWP neuropathologic phenotype. CWPs are predominantly composed of type I Aβ filaments present in two novel arrangements, type Ic and type Id; additionally, CWPs contain type I and type Ib Aβ filaments. Tau filaments have the AD fold, which has been previously reported in sporadic AD and DIAD. The formation of type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. Our data are relevant for the development of PET imaging methodologies to best detect CWPs in DIAD.

棉絮斑块 （CWP） 被描述为显性遗传阿尔茨海默病 （DIAD） 的神经病理表型特征，由早老素 1 （PSEN1） 基因中的一些错义和缺失突变引起。CWP 是圆形的嗜酸性粒细胞性 β 淀粉样蛋白 （Aβ） 斑块，缺乏淀粉样蛋白核心，在硫黄素 S （ThS） 制剂中可识别，但不发出荧光。氨基末端截短和翻译后修饰的 Aβ 肽种类是 CWP 的主要成分。Tau 免疫阳性神经突可能存在于 CWP 中。此外，神经原纤维缠结与 CWP 共存。在此，我们报道了从受 PSEN1 V261I 和 A431E 突变引起的 DIAD 影响的个体的脑组织中分离的 Aβ 和 tau 丝的结构，具有 CWP 神经病理学表型。CWP 主要由 I 型 Aβ 细丝组成，以两种新颖的排列形式存在，即 Ic 型和 Id 型;此外，CWP 含有 I 型和 Ib 型 Aβ 细丝。Tau 丝具有 AD 折叠，这在之前已经在散发的 AD 和 DIAD 中报道过。Ic 型和 Id 型 Aβ 细丝的形成可能是 CWP 表型的基础。我们的数据与 PET 成像方法的开发相关，以最好地检测 DIAD 中的 CWP。