Extended Data Fig. 3: Three subtypes of Lewy body disease.

The SuStaIn algorithm inferred three different patterns of Lewy body disease progression. Maps of Lewy pathology deposition are shown for increasing SuStaIn stages with color codes representing pathology severity (red = mild, purple = moderate, blue = severe, black = very severe). Boxes show the positional variance diagrams, with each box representing the certainty that a region has reached a specific level of pathology at the listed SuStaIn stage, with darker colors representing higher certainty. a. A brain-first subtype with disease initiation in the amygdala and OB, followed by spreading to limbic and upper brainstem regions. Later, the pathology appears in the DMV, SY and cortex. Peripheral tissues only start to become positive when CNS pathology is widely disseminated. b. A parasympathetic body-first type, in which the DMV and LC are the first positive regions. The NBM, SN, and SY follows next and then the amygdala and OB. Peripheral tissue pathology follows soon after and shows robustness much earlier compared to the brain-first subtype. c. A sympathetic body-first type presenting initial pathology in the SY and heart. The SY already shows severe pathology when DMV and adrenal gland pathology appears in SuStaIn stage 5-6. Only later, the LC, amygdala and OB becomes positive followed by the SN and NBM.