Gray Matter Atrophy Associated with Extrapyramidal Signs in the Lewy Body Variant of Alzheimer's Disease

Abstract

Up to 60% of the patients with Alzheimer’s disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has not been studied in the LB variant of AD using structural magnetic resonance imaging (MRI). The purpose of this study was to determine the relationship between patterns of brain atrophy and clinical EPS in patients with pathologically confirmed AD. We compared gray matter structure using voxel-based morphometry in 29 Definite AD cases, 16 (55%) of whom also had LBs identified with α-synuclein immunohistochemistry. Multivariate models analyzed brain volume at a voxel level accounting for subject group, Mini-Mental State Examination (MMSE), EPS, total brain volume, and the time from MRI scan to death. There was no significant difference in gray matter volume in the Definite AD patients as a function of LB. There was a significant association between gray matter volumes and the MMSE in AD patients, both with and without LBs. There was a significant correlation between gray matter volume and EPS only in the group of AD patients with LBs, and not in those with pure AD. These findings suggest that that the etiology of EPS in patients with the LB variant of AD is associated with neuronal loss in the nigrostriatal tracts. By contrast, the source of the EPS in AD alone appears to be less well localized.

Potential biomarkers and novel pharmacological targets in protein aggregation-related neurodegenerative diseases

“…In particular, antibodies that recognize the different toxic species of Aβ can act: i) directly by neutralizing them and blocking their toxic effects; ii) by stimulating microglial clearance; and/or iii) by promoting Aβ exit from the brain to the systemic circulation. This therapeutic approach has been demonstrated to decrease brain Aβ levels, reduce gliosis and neuritic dystrophy, and counteract memory impairment in AD transgenic mice [156]. More importantly, Alzheimer's disease patients who were immunized with aggregated Aβ showed diminished cognitive decline and slowed disease progression compared with patients who received the placebo [157].…”

Does the oxysterol 27-hydroxycholesterol underlie Alzheimer's disease–Parkinson's disease overlap?

“…However, a large number of AD patients also have α-synuclein deposition and a subset of PD population accumulates Aβ in the brain. The distribution of Lewy bodies in AD occurs mostly in the amygdala, where Lewy bodies are observed in approximately 60% of both sporadic and familial AD (Kotzbauer et al, 2001; Choi et al, 2012). This overlap strongly suggest that specific pathological pathways converge to trigger common hallmarks of both AD and PD in same brain.…”

Inhibitors of protein aggregates as novel drugs in neurodegenerative diseases

“…In particular, antibodies that recognize Aβ toxic species have been developed to bind and neutralize them; otherwise, the antibodies can stimulate microglial clearance, or induce Aβ exit from the brain [51][52][53][54][55][56][57].…”