Lewy body variant of Alzheimerʼs disease

Abstract

The contribution of alpha-synuclein accumulation in Alzheimer's disease (AD) plaques is currently a matter of scientific debate. In the present study antisera against the N- and C-terminus, the full-length protein and the central so-called non-amyloid component (NAC) domain of the alpha-synuclein protein were used to address this question in brains of cases with typical AD and of cases with the Lewy body (LB) variant of AD. In typical AD cases, none of the antisera revealed evidence for co-accumulation of alpha-synuclein with extracellular A beta peptides in plaques or in dystrophic neurites decorating the plaque core. Interestingly, cases with mixed pathology of the LB variant of AD revealed accumulation of alpha-synuclein in LBs and in dystrophic neurites of A beta plaques.

Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

“…Discrepancies in prior findings regarding LBD and neurofibrillary tangles, in which some studies found positive associations (Iseki et al., 2003; Jellinger and Attems, 2008; Sonnen et al, 2010) while others did not (Chung et al, 2015; Kotzbauer et al, 2012; Obi et al, 2008; Schneider et al., 2012) may be accounted for by the non-monotonic association we observed between cortical LBD and level of ADNC. Interactions between amyloid and α-synuclein may lead to an alternative pathologic and clinical presentation than ADNC only, in which neurofibrillary tangles are more predominant (Jellinger and Attems, 2008; Swirski et al, 2014; Wirths et al, 2000). …”

“…Vascular brain injury (VBI) and Lewy body disease (LBD) commonly co-occur with Alzheimer’s disease neuropathologic change (ADNC) in older adults (Wirths et al, 2000; Riekse et al, 2004; Rahimi and Kovacs, 2014). Pre-mortem cognitive impairment is associated with mixed neuropathologies at autopsy (Schneider et al, 2007; Montine et al, 2012; Kawas et al, 2015; White et al, 2016).…”

Mixed neuropathologies and estimated rates of clinical progression in a large autopsy sample

“…ADNP in more severe stages may overwhelm the effects of VBI [11,12]. Lewy body disease (LBD) and ADNP also commonly coexist [13–16] and are associated with cognitive decline [17,18]. Lewy body development may be enhanced by ADNP [13,19].…”

“…Lewy body disease (LBD) and ADNP also commonly coexist [13–16] and are associated with cognitive decline [17,18]. Lewy body development may be enhanced by ADNP [13,19]. Only one study reported testing whether concomitant LBD modified the association between ADNP and cognition, but they found no significant interactions [16].…”

Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aβ accumulation

“…Fundamental axonal pathology in AD includes the aberrant accumulation of various proteins in abnormal swollen axons, including APP (Cras et al, 1991), synaptic proteins like alpha-synuclein (Wirths et al, 2000), glycogen (Mann et al, 1987), as well as the occurrence of abnormal paired helical filaments (PHFs) (Praprotnik et al, 1996). With the implementation of new imaging techniques, it has been recently shown in in-vivo studies that impairment of axonal transport mechanisms and decreased axonal transport rates might have a significant impact on the pathogenesis of AD already early in the disease process (Smith et al, 2003; Teipel et al, 2007; Cross et al, 2008; Minoshima and Cross, 2008).…”