Table 2.
Summary of relevant neuropathological evidence of Lewy-type co-pathology in Alzheimer’s disease
| Reference | Year | Sample | Main outcomes | Main findings | Comments |
| Leverenz et al. [34] | 1986 | 40 sporadic AD | Neuronal loss, Lewy bodies, or neurofibrillary tangles in the substantia nigra | 18 patients had > 1 of these changes | Pre-α-synuclein studies |
| 13 of them had featured rigidity+/- tremor | |||||
| 9 had had a second diagnosis of PD | |||||
| 11 (85%) had PD pathologic changes | |||||
| Ditter et al. [35] | 1987 | 20 sporadic AD | Lewy body formation, neuronal loss, and gliosis of pigmented nucleiControlled for use of neuroleptic medication | 11 cases (55%) showed PD changes | |
| No significant difference in age or symptom duration in AD+PD vs. AD-PDHistory of rigidity in 80% of AD+PD but only 14% of AD-PD | |||||
| Tremor not observed in either AD+PD or AD-PD | |||||
| Lippa et al. [4] | 1998 | 74 cases of familial AD | Immunohistochemistry with antibodies to α/β/γ-synuclein | In at least in 22% of the entire cohort there were α-synuclein-immunoreactive Lewy bodies. In 12 of the 19 fAD cases (63%), in which the amygdala was investigated, Lewy bodies were found in this structure | First study investigating using α-synuclein immunohistochemistry in a large cohort of fAD |
| Lippa et al. [36] | 1999 | 20 Down’s syndrome | Immunohistochemistry with antibodies to α/β/γ-synuclein | Many α-synuclein+Lewy bodies and neurites in 50% of amygdala samples with Alzheimer pathologyNo positivity for β or γ synuclein | First study using α-synuclein immunohistochemistry in Down’s syndrome cases with Alzheimer pathology |
| Hamilton et al. [4] | 2000 | 145 sporadic AD | Immunohistochemistry with antibodies to α-synuclein | Lewy bodies found in 88/145 (60.7%) of CERAD cases and 56.8% of 95 cases with Braak stage 5-6) | First large study using α-synuclein immunohistochemistry in late onset sporadic AD cases |
| The amygdala was severely involved in all cases | |||||
| Absent to mild Lewy pathology in the substantia nigra | |||||
| Arai et al. [5] | 2001 | 27 sporadic AD | Relationship between Alzheimer pathology and α-synuclein aggregation | 13 of 27 cases (48.2%) had α-synuclein+structures including Lewy bodies | No direct correlation between Alzheimer and Lewy lesions, but Lewy pathology present even in cases and locations with more severe tau degeneration (hippocampus) |
| Frequency and density of plaques and tangles did not differ between+and – cases | |||||
| α-synuclein+structures most frequent in the amygdala | |||||
| α-synuclein+structures different from Lewy bodies more frequent in the hippocampus | |||||
| Lewy-related structures even in AD cases with widespread and numerous tangles | |||||
| Fujishiro et al. [37] | 2008 | 41AD with amygdala Lewy bodies (AD-ALB)21 AD without ALB | α-synuclein pathology in the olfactory bulb in AD with and without ALB | α-synuclein pathology detected in the olfactory bulb in 38/41 AD+ALB (93%) and 4 of 21 AD-ALB (19%) | Co-localization of tau and α-synuclein in the olfactory bulb |
| Double immunolabeling revealed co-localization of tau and α-synuclein in neurons and neurites of the olfactory bulb | |||||
| Savica et al. [38] | 2019 | 32 DLB/AD, 54 ADLB, 70 AD, 41 PDD/AD cases | AD subjects with LTS pathology had higher UPDRS II and III total scores as well as generally higher individual scores compared to AD alone | Prospective design | |
| Depression scales and Trail-making Test A correlated significantly with LTS |
AD, Alzheimer’s disease; AD-ALB, Alzheimer’s disease with amygdala Lewy bodies; ADLB, AD cases with LTS, but not meeting the criteria of DLB; DLB, dementia with Lewy bodies; fAD, familial Alzheimer’s disease; LTS, Lewy-type synucleinopathy; PD, Parkinson’s disease; PDD, Parkinson’s disease dementia.