DLB vs PDD vs MSA imaging / pathology rows (VMAT PET / sMRI Burton-Borroni-Cohn / aSyn PET DWI Pellecchia / Synuclein-only inclusions Olivera 2021 / Aβ load Hepp 2018 / NFT / Brainstem-Limbic-neocortical / Chia 2021 GWAS / GBA mutations and MSA)
| DLB | PDD | MSA | |||
|---|---|---|---|---|---|
| imaging | cochrane10 | (Olivera, 2021 #1268) PDII; H&Y(2.4), variable, largely similar degree of deficit | (Jeong, 2017 #1392) | ||
| VMAT PET | markers of dopamine neurodegeneration may not be as closely coupled to successful treatment. (Wild, 2009 #1395) high | ||||
| sMRI | (Burton, 2002 #1132) n=25, 75 y, disease duration 36.4. MMSE 13.3 / GM volume in Frontal, temporal & insular cortex (vs PD) (Borroni, 2015 #1133) postmortem; thinning of the parietal and occipital cortices (28). (Ohn, 2023 #2462677) cortical thinning in the temporoparietal, mesial temporal lobe and lateral occipital cortices has been characterized in DLB [8, 9] | (Borroni, 2015 #1133) postmortem; frontal cortex thinning | |||
| aSyn PET DWI | (Pellecchia, 2011 #1351) longitudinal (12 m Fwh, n=11), - A rate of progression of Tracer (Da-) percent change versus baseline - was observed in the pone (10.7% vs 6.3%) and putamen (4.8% vs 6.7%). - Percent changes of UPDRS Part III and UMSARS Part II disease duration did not correlate with percent changes of Tracer (Da-) in any brain region. | ||||
| pathology | SN loss in majority (Outeiro, 2019 #1111) Massive presynaptic small αSYN (mostly) aggregates in different from LB) with complete loss of dendritic spines at presynaptic (postmortem) (Kramer, 2007 #1318) (postmortem) Neocortex atrophy and limbic system (Outeiro, 2019 #1111), relative preserved medial temporal lobe (similar AD) Lee, 2019 #828) The progression of LBs to the limbic and neocortical structures (most notably layers V and VI) is associated with the diagnosis of dementia in DLB and is an indicator for a neuropathological diagnosis of DLB [13] | # 1380meta-analysis of 2002 cases - 8, 372%); from 44 reports. limbic and neocortical aSyn pathology had the strongest association with dementia. - between a 5fold and a third of all PD cases in the largest studies had comorbid AD However: DLB pathology is heterogeneous, including neuronal loss, cholinergic degeneration, AD and vascular pathology in addition to LB pathology (Olivera, 2021) In DLB it is difficult to determine the pattern of spreading as Lewy pathologies occur from the outset in many brain regions, suggesting a more rapid process of spreading potentially due to coexisting AD deposition. Many DLB patients have coexisting AD pathologies, while in DLB patients the pattern of spread of αSyn pathologies is from the periphery into the limbic system and then beyond. α-syn-only inclusions of αSyn are an important features in PD and DLB but observed less frequently in [Sometano, 2019 #1138] fast pathology was moderate or severe in around a third, and Aβ pathology was moderate or severe in over half. Aβ was associated with a more rapid cognitive decline and earlier mortality, and in the striatum, distinguished PDD from DLB. | |||
| Aβ load | (Hepp, 2018 #850 ICN-mediam) AB was more prevalent in DLB than in PDD, and tau tangles appeared to have a synergistic relationship with αSyn, leading to worse prognosis (Hepp, 2018 #1132) (a-4) | ||||
| NFT (mean medium average) | (Hepp, 2018 #1130; 2-3 (a-4) (Hepp, 2018 #1130; 1) (Hepp, 2018 #1130; 1) (a-5) | ||||
| type |
(Jellinger, 2018 #852) 등 가 가만 가가? Both DLB and PDD show heterogeneous pathology and neurochemistry; suggesting that they share important common underlying molecular pathogenesis with AD and other proteinopathies. While we prefer to view DLB and PDD as extremes on a continuum (Walker, 2019 #853) compared frequency of pathologies in LBs (fig2), DLB는 비교 가능한. | ||||
| Brainstem Limbic neocortical |
(Chia, 2021 #1284) large GWAS: 5 genes identified, BIN1 (Bridging Integrator 1, rs617139419-T), TMEM175, SNCA (rs7681440 ↑↑↓), APOE 가만 도 마. (도 가)? So, LBD genetically intersects with AD & PD/ (Huang, 2012 #338) (Hahn, 2013 #822) 7.6% (Synonymous variants and those in the upstream untranslated region) were omitted from the analysis. MSA-P with predominant parkinsonism (MSA-P) | EPS predominate (striatonigral degeneration: parkinsonian variant) MSA-C with cerebellar features (MSA-C) | cerebellar ataxia predominates ('sporadic olivopontocerebellar atrophy') The association of GBA mutations with multiple system atrophy (MSA) is not clear, as some studies showed no association between GBA mutations and MSA, while the largest study so far demonstrated a strong association, albeit weaker than the association with PD or DLB. https://www.gan-orlab.org/glb-associated-synapathies | ||||
| GBA activity | 2014 #1115 / Cross sectional | 3.3e15.3) and in DLB (n=29) (13.8%), ↓ AAO, (Moors, 2019 #1086) postmortem (Parnetti, 2009 #1256) CSF, ↓ (~half) | (Krismer, 2014 #1074) SNCA mutations have not been detected in... |