Table 3.
Summary of LRRK2 autopsy reports
| Report | Autopsies (n) | Genotype (n) | Phenotype (n) | Pattern of Neuronal Loss | LB, LN Pathology (n) | LB Distribution– Braak Stage (n) | Tau Pathology– NFT Stage (n) | Other Inclusions (n) |
|---|---|---|---|---|---|---|---|---|
| Gilks et al., 2005148 | 3 | G2019S (3) | PD (3) | SNpc, LC | 3 | 3 (1) 4 (2) | Sparse (1) − (2) | – |
| Gaig et al., 2008149; Gaig et al., 2007150; Gomez and Ferrer, 2010151 | 3 | G2019S (3) | PD (3) | SNpc, LC | + (2) − (1) | 4 (1) 5 (1) − (1) | I (1) II (1) III (1) | – |
| Rajput et al., 2006152 | 1 | G2019S (1) | PD (1) | SNpc mild | − (1) | – | IV (1) | PSP-like |
| Ross et al., 2006137 | 10 | G2019S (10) | PD (8) dementia (3/8), cognitive decline (2/8) AD (1) control (1) | SNpc, LC | + (8) − (2) | 3 (4) 4 (3) 6 (1) − (2) | − (3) I (1) III (4) AD (2) | – |
| Giasson et al., 2006153 | 3 | G2019S (3) | EOPD (1), PD (2) dementia (1/3) | SNpc, LC | + (2) − (1) | 4 (1) 5 (1) − (1) | I (1) III (1) AD (1) | – |
| Dachsel et al., 2007154 | 1 | G2019S (1) | Dementia (1) | Hippocampus | − (1) | − (1) | − (1) | FTD-U |
| Silveira-Moriyama et al., 2008155 | 4 | G2019S (4) | PD (4) | SNpc, LC, olfactory bulb | 4 | 5 (4) | II (4) | Olfactory bulb LBs (4) |
| Poulopoulos et al., 2012156 | 3 | G2019S (3) | EOPD (2), PD (1) dementia (2/3) | SNpc, LC | 3 | 4 (2) 6 (1) | Sparse (2) AD (1) | |
| Kalia et al 201522 | 2 a, b, c | G2019S | n.d. | n.d. | + (2), − (1) | n.d. | − (3); βAPs present (3) | |
| Vilas et al. 2016157 | 2 | G2019S (2) | PSP (1) | Severe GP, SNpc, subthalamic nucleus | Absent LBs; no alpha-synuclein | n/a | Neuronal and glial subcortical 4-repeat tau | pTau-positive tufted astrocytes; grade A3, B2, C2 AD pathology; No TDP43; coiled bodies; Globose neuronal tangles |
| PD (1) | LBS in cingulate and temporal cortices, amygdala, basal forebrain, SNpc, NC | coiled bodies; tufted astrocytes; Globose neuronal tangles | ||||||
| Wszolek et al., 2004158, Zimprich et al., 200423, Wider et al., 2010159 | 6 | R1441C (4) Y1699C (2) | PD (6) | SNpc LC | + (2/4 R1441C) − (4) | 4 (1) 6 (1) − (4) | Sparse (1), AD (1 Y1699C), − (4) | PSP-like in 1 (R1441C); TDP-43 in SNpc neurites in 1 (R1441C) |
| Khan et al., 2005160 | 1 | Y1699C | PD (1) | SNpc, LC | 1 | 3 (1) | II (1) | Olfactory bulb LBs |
| Giordana et al., 2007161 | 1 | I1371V (1) | PD cognitive decline (1) | SNpc>LC | 1 | 4 (1) | II (1) | – |
| Covy et al., 2009162 | 2 | R793M (1) L1165P (1) | PD (2) dementia (1/2) | SNpc, LC | 2 | 4 (2) | II (1) III (1) | TDP-43 in TC (2) |
| Gaig et al., 2008149 | 1 | R1441R | PD dementia (1) | SNpc | 1 | n.d. | n.d. | – |
| Hasegawa et al., 2009163; Hasegawa and Kowa, 1997164 | 8 | I2020T (8) | PD (8) | SNpc, SNpr, LC spared | − (7) + (1) | − (7) 3 (1) | − (8) | GCI (1) |
| Marti-Masso et al., 2009165 | 1 | R1441G | PD (1) | SNpc>LC | − (1) | – | I (1) | a-B crystalline in SN |
| Puschmann et al., 2011130 | 1 | N1437H (1) | PD (1) | SNpc>LC | 1 | 5 (1) | Sparse (1) | Diffuse, atypical ubiquitin+ inclusions |
| Kalia et al.22, 2015 | 1 d | R1441G | n.d. | n.d. | − (1) | n.d. | − (1) | – |
G2019S mutation carriers are shaded in light gray. Abbreviations: PD = Parkinson’s disease; EOPD = early onset Parkinson’s disease; PSP = progressive supranuclear palsy; FTD-U = frontotemporal dementia with ubiquitin inclusions; LB = Lewy bodies; LN = Lewy neurites; βAPs = β-amyloid plaques; GCI = glial-cytoplasmic inclusions; GP = globus pallidus; SNpc = substantia nigra pars compacta; SNpr = substantia nigra pars reticulata; LC = locus coeruleus; TC = temporal cortex.
Case provided by SM Goldman, B Schüle, J Langston (The Parkinson’s Institute, Sunnyvale, CA, USA)
Case provided by J Aasly (University of Trondheim, Trondheim, Norway; c: Case provided by AE Lang, L Hazrati
Marras (University of Toronto, Toronto, Canada)
Case provided by J Ruiz-Martinez, J Marti Masso, (Hospital Universitario Donostia, CIBERNED, San Sebastián, Spain)