期刊
ACTA NEUROPATHOLOGICA
卷 138, 期 5, 页码 771-782出版社
SPRINGER
DOI: 10.1007/s00401-019-02071-3
关键词
Lewy-related pathology; alpha-Synuclein; Population-based; Aged; 80 and over; Lewy body diseases; Alzheimer's disease
资金
- University of Helsinki including Helsinki University Central Hospital
- Helsinki University Central Hospital
- Academy of Finland [294817]
- Medicinska Understodsforeningen Liv och Halsa rf
- Sigrid Juselius Foundation
- Finska Lakaresallskapet
- Finnish Cultural Foundation
- Helsingin ja Uudenmaan Sairaanhoitopiiri [TYH2018217]
- MRC [G0502157, G0900652, G0400074, G1100540] Funding Source: UKRI
- Academy of Finland (AKA) [294817, 294817] Funding Source: Academy of Finland (AKA)
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 LRP forms a distinct type of alpha-synucleinopathy, where LRP originates in the amygdala. The frequency of distinct forms of LRP progression types has not been studied in a population-based setting. We investigated the distribution and progression of LRP and its relation to AD pathology and apolipoprotein (APOE) epsilon 4 in a population-based sample of Finns aged over 85 years (N = 304). Samples from spinal cord to neocortical areas representing 11 anatomical sites without any hierarchical selection were analyzed immunohistochemically (alpha-synuclein antibody clone 5G4). LRP was present in 124 individuals (41%) and according to DLB Consortium guidelines 19 of them were categorized as brainstem, 10 amygdala-predominant, 41 limbic, and 43 diffuse neocortical type, whereas 11 could not be classified. To determine the LRP progression patterns, a systematic anatomical scoring was carried out by taking into account the densities of the semiquantitative LRP scores in each anatomic site. With this scoring 123 (99%) subjects could be classified into two progression pattern types: 67% showed caudo-rostral and 32% amygdala-based progression. The unsupervised statistical K-means cluster analysis was used as a supplementary test and supported the presence of two progression patterns and had a 90% overall concordance with the systematic anatomical scoring method. Severe Braak NFT stage, high CERAD score and APOE epsilon 4 were significantly (all p < 0.00001) associated with amygdala-based, but not with caudo-rostral progression type (all p > 0.2). This population-based study demonstrates two distinct common LRP progression patterns in the very elderly population. The amygdala-based pattern was associated with APOE epsilon 4 and AD pathology. The results confirm the previous progression hypotheses but also widen the concept of the AD-associated LRP.
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