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Introduction: Depletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer's disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hypertrophy and 'hyperinnervates' the surviving cholinergic neurons. Galanin is considered as a highly inducible neuroprotective factor and in AD this is assumed to be part of a protective tissue response. The aim of this study was to determine if a similar galanin upregulation is present in the nbM in post-mortem tissue from patients with LBD. Gallatin immunohistochemistry was carried out on anterior nbM sections from 76 LBD cases (27 PD, 15 PD with mild cognitive impairment (MCI), 34 PD with dementia (PDD) and 4 aged-matched controls. Galaninergic innervation of cholinergic neurons was assessed on a semi-quantitative scale., Results: The LBD group had significantly higher galaninergic innervation scores (p = 0.016) compared to controls. However, this difference was due to increased innervation density only in a subgroup of LBD cases and this correlated positively with choline acetyltransferase-immunopositive neuron density., Conclusion: Galanin upregulation within the basal forebrain cholinergic system in LBD, similar to that seen in AD, may represent an intrinsic adaptive response to neurodegeneration that is consistent with its proposed roles in neurogenesis and neuroprotection.

Background: Microglial activation is a pathological feature common to both Alzheimer's and Parkinson's diseases (AD and PD). The classical activation involves release of pro-inflammatory cytokines and reactive oxygen species. This is necessary for maintenance of tissue homeostasis and host defense, but can cause bystander damage when the activation is sustained and uncontrolled. In recent years the heterogeneous nature of microglial activation states in neurodegenerative diseases has become clear and the focus has shifted to alternative activation states that promote tissue maintenance and repair. We studied the distribution of CD163, a membrane-bound scavenger receptor found on perivascular macrophages. CD163 has an immunoregulatory function, and has been found in the parenchyma in other inflammatory diseases e.g. HIV-encephalitis and multiple sclerosis. In this study, we used immunohistochemistry to compare CD163 immunoreactivity in 31 AD cases, 27 PD cases, and 16 control cases. Associations of microglia with pathological hallmarks of AD and PD were investigated using double immunofluorescence., Results: Parenchymal microglia were found to be immunoreactive for CD163 in all of the AD cases, and to a lesser extent in PD cases. There was prominent staining of CD163 immunoreactive microglia in the frontal and occipital cortices of AD cases, and in the brainstem of PD cases. Many of them were associated with Aß plaques in both diseases, and double staining with CD68 demonstrates their phagocytic capability. Leakage of fibrinogen was observed around compromised blood vessels, raising the possibility these microglia might have originated from the periphery., Conclusions: Increase in microglia's CD163 immunoreactivity was more significant in AD than PD, and association of CD163 immunoreactive microglia with Aβ plaques indicate microglia's attraction towards extracellular protein pathology, i.e. extracellular aggregates of Aβ as compared to intracellular Lewy Bodies in PD. Double staining with CD163 and CD68 might point towards their natural inclination to phagocytose plaques. Fibrinogen leakage and compromise of the blood brain barrier raise the possibility that these are not resident microglia, but systemic macrophages infiltrating the brain.

Background: The role of both microglial activation and alpha-synuclein deposition in Parkinson's disease remain unclear. We have tested the hypothesis that if microglia play a primary role in Parkinson's disease pathogenesis, the microglial "activated" phenotype should be associated with histopathological and/or clinical features of the disease., Methods: We have examined microglial MHC class II expression, a widely used marker of microglial activation, the occurrence of CD68-positive phagocytes and alpha-synuclein immunoreactivity in post-mortem human substantia nigra affected by idiopathic Parkinson's disease (PD). Using semi-quantitative severity ratings, we have examined the relationship between microglial activation, alpha-synuclein deposition, classical neuropathological criteria for PD, subtype of the disease and clinical course., Results: While we did not observe an association between microglial MHC class II expression and clinical parameters, we did find a correlation between disease duration and the macrophage marker CD68 which is expressed by phagocytic microglia. In addition, we observed a significant correlation between the degree of MHC class II expression and alpha-synuclein deposition in the substantia nigra in PD., Conclusion: While microglia appeared to respond to alpha-synuclein deposition, MHC class II antigen expression by microglia in the substantia nigra cannot be used as an indicator of clinical PD severity or disease progression. In addition, a contributory or even causative role for microglia in the neuronal loss associated with PD as suggested by some authors seems unlikely. Our data further suggest that an assessment of microglial activation in the aged brain on the basis of immunohistochemistry for MHC class II antigens alone should be done with caution.