Table 6.
Summary of GBA 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) |
|---|---|---|---|---|---|---|---|---|
| Tayebi et al. 200383; Wong et al. 200484; Goker-Alpan et al. 201085 | 4 GD (type 1) | N370S/N370S (2), N370S/? (1) D409H/L444P+ duplication (1) | PD Dementia (4) | SNpc, CA2–4, calcarine layer 4b, cortical layer 5 | + (4), especially CA2–4 | 5 to 6 (2) 3 (1) 4 (1) | No details | Gaucher cells (4) GBA-reactive LB inclusions (3) Glucosylsphingosine levels as in controls |
| Lwin et al. 200487 | 2 GD 10 GBA heterozygotes | N370S/N370S (2), T369M (3), N370S (3), L444P (1), K198T (1), R329C (1), E326K (1) | PD (12) EOPD (2/12, 1 GD, 1 heterozygote), dementia (most) | No details | + (10) — (2) E326K and K198T carriers | 6 (2 GD, 5 GBA heterozygotes), 4 (3 GBA heterozygotes) | No details | Enzyme activity: 7% to 11% in 2 GD, 43% to 100% in 10 GBA heterozygotes |
| Eblan et al. 200589 | 2 GBA heterozygotes | D140H (1) RecNciI (1) | PD (2) | No details | 2 | No details | No details | No details |
| Goker-Alpan et al. 200682, 201085 | 9 GBA heterozygotes | N370S (5) R120W (1) A359X (1) T267I (1) I161N (1) | PD dementia (9) | No details | 9 | 6 (8) 4 (1) | AD (6) — (3) | GBA-reactive LB inclusions (4) |
| Mata et al. 200888 | 2 GBA heterozygotes | L444P (1) N370S (1) | PD dementia (2) | No details | 2 | 6 (2) | V (1) II (1) | No details |
| Clark et al. 200976 | 1 GD (with AD) | N370S/N370S (1) | AD | |||||
| 31 GBA heterozygotes, 2 homozygote/compound heterozygotes of mutations of unclear significance | N370S (9) T369M (4) E326K (4) 84gg (1) H255Q (1) D409H (1) L444P (1) R463C(1) R496H(1) W184R (1) E388K (1) E326K/N188R/S196P/V191G (1) T369M/T369M (1) | PD (27) EOPD (1/27) dementia (no data) | No details | 27 | 4 to 6 (26) 3 (1) | AD (5) | No details | |
| G1444 A>G (1) P171P (1) T369M (2) G389V (1) | AD (5) | |||||||
| T369M (1) | Normal (1) | |||||||
| Farrer et al. 200991 | 8 GBA heterozygotes | H255Q (1), IVS2 +1 G>A (1), 1263–1317del (1), E326K (5) | PD (8) dementia (6) | No details | 8 | 5 to 6 (6) 4 (2) | No details | No details |
| Neumann et al. 200990 | 17 GBA heterozygotes | L444P (6), N370S (3), R463C (3), D409H (1), R131C (1), C193E (1), RecNcil (1), RecA456P (1) | PD (16), EOPD (1/16), dementia (9/16), MSA (2/16), no data (1) | SNpc, LC | 17 | 5 to 6 (17) | >III (2) | No details |
| Segarane et al. 200980 | 1 GBA heterozygote | R262H | MSA | No details | No details | No details | No details | No details |
| Nishioka et al. 201181 | 3 GBA heterozygotes, 1 homozygote of a mutation of unclear significance | N370S (1), L444P (1), E388K (1), A292T/A292T (1) | PD (4) dementia (4) | No details | 4 | 5 to 6 (4) | No details | No details |
| Sklerov et al. 201795 | 1 GBA homozygote | N370S | MSA | No LBs | Diffuse GCIs; Rare neurofibrillary tangles | |||
| 3 GBA heterozygotes | T369M (1), N370S (1), R496H (1) | MSA | Occasional neurons labeled with anti-synuclein antibodies, without LBs | Neuropils, no neuritic plaques | Diffuse GCIs; Rare neurofibrillary tangles |
Gaucher disease (GD) patients are shaded in light gray, GBA heterozygotes are shaded in white. Abbreviations: AD = Alzheimer’s dementia; EOPD = early-onset PD, GCI, glial-cytoplasmic inclusions; GD = Gaucher disease, LB = Lewy body; LN = Lewy neurites; MSA = multiple system atrophy; PD = Parkinson’s disease