P1-423: alzheimer's disease associated lewy related pathology arises from amygdala

Lewy related pathology (LRP) follows hierarchical caudo-rostral progression in dementia with Lewy bodies, according to the Braak hypothesis (Braak & Braak, 1991). LRP is also frequently present in combination with Alzheimer's disease (AD). The LRP pathology in AD is often most severe in amygdala, and a hypothesis of LRP arising in amygdala and then progressing to entorhinal cortex, brainstem or both, has also been proposed (Uchikado et al., 2006, Dickson et al., 2010). Here we investigated the distribution of LRP and its relation to AD pathology in a population-based sample of Finns aged over 85 years (N=304), using a wide distribution of tissue samples from spinal cord to neocortical areas without any hierarchical selections. The LRP was assessed immunohistochemically with mouse monoclonal anti-alpha-synuclein antibody (clone 5g4) on eleven tissue sections per individual. We categorized individuals into LRP types (brainstem-predominant, amygdala-predominant, limbic, and diffuse neocortical) according to DLB Consortium guidelines. Thenwe studied if individuals could be consistently divided into caudo-rostral progression and amygdala arising progression categories by 1) expert analysis taking into account differences in density and distribution profiles of the semiquantitative LRP scores and 2) by statistical K-means cluster analysis.The LRP data was compared with the CERAD and Braak NFT scores, and APOEgenotypes. Any LRP was found in 124 individuals (41%). 43 were classified as neocortical type, 41 as limbic, 19 as brainstem, 10 as amygdala-predominant, while 11 were non-classifiable, based on the DLB Consortium guidelines. Expert analysisindicated two distinct pathological profiles of progression, and K-means cluster analysis supported the classification of individuals into two clusters: 73 (59 %) subjects showed caudo-rostral progression and 39 (31 %) amygdala arising progression. Severe Braak NFT stage, high CERAD score and APOE e4 were significantly (p<0.001) associated with amygdala arising progression but not with caudo-rostral progression. Our data demonstrate two distinct LRP progression patterns in the very elderly population, and support previous hypotheses on LRP progression. The amygdala arising pattern was strongly associated with AD neuropathology and APOE e4, while the caudo-rostral pattern did not associate with these.