Early‐onset Dementia with Lewy Bodies

Abstract

The clinical and neuropathological characteristics of an atypical form of dementia with Lewy bodies (DLB) are described. The proband experienced difficulties in her school performance at 13 years of age. Neurological examination revealed cognitive dysfunction, dysarthria, parkinsonism and myoclonus. By age 14 years, the symptoms had worsened markedly and the proband died at age 15 years. On neuropathological examination, the brain was severely atrophic. Numerous intracytoplasmic and intraneuritic Lewy bodies, as well as Lewy neurites, were present throughout the cerebral cortex and subcortical nuclel; vacuolar changes were seen in the upper layers of the neocortex and severe neuronal loss and gliosis were evident in the cerebral cortex and substantia nigra. Lewy bodies and Lewy neurites were strongly immunoreactive for alpha-synuclein and ubiquitin. Lewy bodies were composed of filamentous and granular material and isolated filaments were decorated by alpha-synuclein antibodies. Immunohistochemistry for tau or beta-amyloid yielded negative results. The etiology of this atypical form of DLB is unknown, since there was no family history and since sequencing of the exonic regions of alpha-Synuclein, beta-Synuclein, Synphilin-1, Parkin, Ubiquitin C-terminal hydrolase L1 and Neurofilament-M failed to reveal a pathogenic mutation. This study provides further evidence of the clinical and pathological heterogeneity of DLB.

Unusual α‐synuclein and cerebellar pathologies in a case of hereditary myoclonus‐dystonia without SGCE mutation

“…The presence of α‐synuclein pathology, neuronal loss and vacuolar change is of interest for several reasons. These pathologies to date have not been noted in cases of primary myoclonus or dystonia, although have been reported in a range of neurodegenerative disorders with coexisting myoclonus, including cases with Parkinson's disease [9], dementia with Lewy bodies [10] and Alzheimer's disease [11]. Our case did not reach criteria for any of these diseases, in particular for pathological Parkinson's disease due to the absence of substantia nigra cell loss.…”

Pathological Changes in Dopaminergic Nerve Cells of the Substantia Nigra and Olfactory Bulb in Mice Transgenic for Truncated Human α-Synuclein(1–120): Implications for Lewy Body Disorders

“…How truncated ␣-synuclein can be generated in cells, under pathological conditions, is currently unclear; the proteasome could be involved (Tofaris et al, 2001;Liu et al, 2003). Isolated ␣-synuclein filaments from human brain are made of the full-length protein, suggesting that truncation may occur after assembly (Spillantini et al, 1998a,b;Crowther et al, 2000;Takao et al, 2004). This notwithstanding, it is clear that the C-terminal region of ␣-synuclein, which binds dopamine derivatives (Norris et al, 2005), is a negative regulator of self-assembly.…”

Alpha- and Gamma-Synuclein Proteins Are Present in Cerebrospinal Fluid and Are Increased in Aged Subjects with Neurodegenerative and Vascular Changes

“…Since in LBD there is, in general, an extensive gliosis both in neo-and subcortical areas irrespective of AD neuropathology [39,40] , and some Lewy body-bearing neurons contain NF-kappaB [41] (a transcriptional factor activated by cytokines, also associated with an increase in microglia), the elevated level of CSF ␥ -synuclein may be a marker of underlying gliosis, similar to the level of GFAP. However, since GFAP appears to be non-specifically upregulated in CSF in numerous neurological disorders (including neurodegenerative disorders, hydrocephalus, subarachnoid haemorrhage and traumatic brain injury) [42] , it will be of interest to determine whether levels of GFAP in CSF do correlate with the levels of ␥ -synuclein we have observed in LBD patients.…”