Selective hippocampal neuron loss in dementia with Lewy bodies

Abstract

Hippocampal volume and neuron number were measured using stereological techniques in pathologically confirmed dementia with Lewy bodies (n = 8), Parkinson's disease only (n = 4), and controls (n = 9). We, and others, have previously shown considerable cell loss in the CA1 and subiculum subregions in Alzheimer's disease. In contrast, these regions were spared in dementia with Lewy bodies where a selective loss of lower presubiculum pyramidal neurons was found. These findings suggest a selective loss of frontally projecting hippocampal neurons in dementia with Lewy bodies versus those projecting to temporal lobe regions in Alzheimer's disease.

α-Synuclein Alters Notch-1 Expression and Neurogenesis in Mouse Embryonic Stem Cells and in the Hippocampus of Transgenic Mice

“…Although most studies focus on dopaminergic neurons, a growing number of reports have shown that other subcortical neuronal populations are affected in PD as well, such as pyramidal neurons in the hippocampus and neocortex of the brains of patients with LBD (Harding et al, 2002;McKeith et al, 2004). In addition, ␣-syn accumulation in the limbic system has been shown to interfere with neurogenesis in the hippocampus and olfactory bulb in aged adult ␣-syn tg mice (Winner et al, 2004(Winner et al, , 2007.…”

“…Recent evidence indicates that abnormal accumulation of misfolded ␣-syn in the synaptic terminals and axons plays an important role (Iwatsubo et al, 1996;Hashimoto and Masliah, 1999;Lansbury, 1999;Hashimoto et al, 2004;Kramer and Schulz-Schaeffer, 2007). Neurodegeneration in these disorders affects primarily the striatonigral system, but, in cases with cognitive impairment, there is more widespread degeneration including neuronal populations in the striatum, hippocampus, and neocortex (Harding et al, 2002;McKeith et al, 2004). Moreover, recent evidence suggests that accumulation of ␣-syn in the limbic system might contribute to the neurodegenerative phenotype by interfering with adult neurogenesis (Winner et al, 2004(Winner et al, , 2007.…”

α-Synuclein Induces Alterations in Adult Neurogenesis in Parkinson Disease Models via p53-mediated Repression of Notch1

“…Neuropathologically, PD is characterized by the loss of dopaminergic neurons mainly in the substantia nigra pars compacta accompanied by the formation of intracytoplasmic inclusions known as Lewy bodies, containing ␣-synuclein (␣-syn) (2,3). Whereas neurodegeneration in PD affects primarily the striatonigral system (4), more widespread degeneration is observed in cases with cognitive impairment, affecting neuronal populations in the striatum, hippocampus, and neocortex (5,6). Accumulation of ␣-syn in these structures affects nonmotor functions such as neurogenesis and olfaction (7), contributing to PD pathology.…”

High Resolution Imaging of the Medial Temporal Lobe in Alzheimer's Disease and Dementia with Lewy Bodies

“…Kenny and colleagues [10] measured the entorhinal cortex using a region of interest on T1 weighted images and found comparable atrophy in AD and DLB. Neuropathological studies have found Lewy bodies neurites preferentially in the CA2 and CA3 region [11,12], though Harding [13] found no difference between control and DLB in any hippocampal subregion volume.…”