Lewy-related pathology exhibits two anatomically and genetically distinct progression patterns: a population-based study of Finns aged 85+

摘要: According to a generally accepted concept Lewy-related pathology (LRP) follows hierarchical caudo-rostral progression. LRP is also frequently present concomitantly with Alzheimer’s disease (AD), and it has been hypothesized that AD-associated forms distinct type of α-synucleinopathy, where originates in the amygdala. The frequency progression types not studied population-based setting. We investigated distribution its relation AD apolipoprotein (APOE) e4 sample Finns aged over 85 years (N = 304). Samples from spinal cord neocortical areas representing 11 anatomical sites without any selection were analyzed immunohistochemically (α-synuclein antibody clone 5G4). was 124 individuals (41%) according DLB Consortium guidelines 19 them categorized as brainstem, 10 amygdala-predominant, 41 limbic, 43 diffuse type, whereas could be classified. To determine patterns, systematic scoring carried out by taking into account densities semiquantitative scores each anatomic site. With this 123 (99%) subjects classified two pattern types: 67% showed 32% amygdala-based unsupervised statistical K-means cluster analysis used supplementary test supported presence patterns had 90% overall concordance method. Severe Braak NFT stage, high CERAD score APOE significantly (all p   0.2). This study demonstrates common very elderly population. associated pathology. results confirm previous hypotheses but widen LRP.