Table 5.
Summary of all genetic autopsy reports
| Gene | Locus | Mode of inheritance |
Autopsies (n)1 | PD phenotype (n) |
Pattern of neuronal loss (n) |
LB, LN pathology (n) |
LB distribution-Braak stage (n) |
Tau pathology-NFT stage (n) |
Other inclusions (n) |
|---|---|---|---|---|---|---|---|---|---|
| SNCA (PARK1/4) | 4q21– q227 | AD | 19 | EOPD (14/19) Dementia (16/19) Autonomic (6/19) |
SNpc, LC (19) Hippocampus (13/19) |
+ (19) | 5–6 (19) | None (11) I–IV (8) | GCI (5) TDP-43 (1) |
| LRRK2 (PARK8) G2019S | 12p11.2–q13.146 | AD | 28 (25 parkinsonism, 1 FTD, 1 AD, 1 control) | EOPD (3/27) Dementia (6/27) |
SNpc, LC (25) | + (22) − (6) |
3 (5) 4 (13) 5 (2) 6 (2) |
None (6) I–II (16) III–IV (1) AD (4) PSP-like (1) |
PSP-like (1) FTLD-U (1) |
| LRRK2 non-G2019S | 21 | Dementia (3/21) | SNpc, LC (21) | + (9) − (12) |
3 (2) 4 (4) 5 (1) 6 (1) No data (1) |
None (12) I–III (7) AD (1) No details (1) |
PSP-like (1) TDP-43 (3) |
||
| Parkin (PARK2) | 6q25.2–27 | AR | 9 | EOPD (8/9) | SNpc>LC (7/9) SNpc equal to LC (2/9) SNpr (2/9) |
+ (2) − (7) |
3,4 (2) | III (1) − (8) |
Thorn-shaped astrocytes (2) LB-like in anterior horn cells (1) |
| PINK1 (PARK6) | 1p35–p36111 | AR | 1 | EOPD, psychosis | SNpc, nbM (LC spared) | + | 4 (1) | - | - |
| DJ-1 (PARK7) | 1p3681 | AR | 0 | ||||||
| GBA2 carriers | 1q2185 | 80 (79 PD, and 1 MSA) | EOPD (3/79) Dementia (25/34); data not available n=45 |
SNpc, LC (17) No details (62) |
+ (77) − (2) |
4–6 (74) 3 (1) No data (2) |
− (3) II–V (4) AD (11) No data (62/80) |
GBA reactive LBs (4) MSA (1) |
|
| GD2 | AR | 10 | EOPD (3/10) Dementia (10) |
SNpc, CA2–4, 5th cortical layer (8) No data (2) |
+ (10)2 | 4–6 (5) 3 (1) No data (4) |
No data | Gaucher cells (4) GBA reactive LBs (3) |
Abbreviations. LB: Lewy body, LN: Lewy neurite, NFT: Neurofibrillary tangle, EOPD: early-onset PD, SNpc: substantia nigra pars compacta, SNpr: Substantia nigra pars reticulata, LC: locus coeruleus, nbM: nucleus basalis of Meynert, AD: Alzheimer’s disease, PSP: progressive supranuclear palsy, GCI: glial-cytoplasmic inclusions, GB: glucocerebrosidase, TDP-43: TAR DNA binding protein-43.
1
All autopsies are from patients with a clinical diagnosis of PD unless otherwise noted.
2
GBA carriers’ autopsies of patients without parkinsonism were not included