Lewy bodies (LBs) appear in the brains of nondemented individuals and also occur in a range of
neurodegenerative disorders, such as
dementia with Lewy bodies (DLB) and
Parkinson's disease. A number of people with a definite diagnosis of
Alzheimer's disease (AD) also exhibit these intraneuronal inclusions in allo- and/or neocortical areas. The latter, referred to as Lewy body variant of AD (LBV), bears a clinical resemblance to AD in terms of age at onset, duration of illness,
cognitive impairment, and illness severity. Since the presence of LBs is accompanied by neuronal cytoskeleton changes, it is possible that the latter may influence neuronal connectivity via alterations to the synaptic network. To address this, we examined the expression of synaptic
proteins (
synaptophysin,
syntaxin, SNAP-25, and
alpha-synuclein) and two
cytoskeletal proteins (tau and MAP2) in the brain tissue of subjects enrolled in a population-based autopsy study (n = 47). They were divided into groups with no memory problems (control group, n = 15), LBV (n = 5), AD devoid of LBs (n = 17), cerebrovascular
dementia (n = 3), and
mixed dementia (n = 7). The LBV and AD groups had a similar degree of
cognitive impairment and neuropathological staging in terms of Braak staging and CERAD score. In comparison with the control group and the
dementia groups without LBs, the LBV group had significantly lower levels of
syntaxin and SNAP-25 (23%) in the neocortex, and depletion of MAP2 (64%), SNAP-25 (34%), and
alpha-synuclein (44%)
proteins in the medial temporal lobes. These findings suggest that the
t-SNARE complex deficit present in LBV may be associated with the presence of LB-related pathology and may explain the more profound
cholinergic loss seen in these patients.