Amyloid-ß peptide protects against microbial infection in mouse and worm models of Alzheimer's disease.

The amyloid-ß peptide (Aß) is a key protein in Alzheimer's disease (AD) pathology. We previously reported in vitro evidence suggesting that Aß is an antimicrobial peptide. We present in vivo data showing that Aß expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. We show that Aß oligomerization, a behavior traditionally viewed as intrinsically pathological, may be necessary for the antimicrobial activities of the peptide. Collectively, our data are consistent with a model in which soluble Aß oligomers first bind to microbial cell wall carbohydrates via a heparin-binding domain. Developing protofibrils inhibited pathogen adhesion to host cells. Propagating ß-amyloid fibrils mediate agglutination and eventual entrapment of unatttached microbes. Consistent with our model, Salmonella Typhimurium bacterial infection of the brains of transgenic 5XFAD mice resulted in rapid seeding and accelerated ß-amyloid deposition, which closely colocalized with the invading bacteria. Our findings raise the intriguing possibility that ß-amyloid may play a protective role in innate immunity and infectious or sterile inflammatory stimuli may drive amyloidosis. These data suggest a dual protective/damaging role for Aß, as has been described for other antimicrobial peptides.

Disease-associated differences in religious cognition in patients with Parkinson's disease.

OBJECTIVE: We sought to establish whether patients with Parkinson's disease (PD) exhibit change in religiosity as a function of disease progression and asymmetry, medication regimens, mood dysfunction, sex, and age. METHOD: We assessed both controlled (conscious reflection) and automatic (semantic priming) modes of religiosity. In the main study, self-reported religiosity, cognitive, and clinical measures were assessed in 71 patients with midstage PD and 75 age-matched controls with non-neurological chronic health conditions. To understand a potential mechanism associated with change in religiosity in PD patients, we supplemented the findings with pilot investigations. The pilot included 21 PD patients and utilized a different self-report measure than that of the main study and assessed automatic activation of religious concepts both on and off levodopa. RESULTS: The main study results demonstrated that PD patients consistently scored lower in five of six dimensions of religiosity. Multivariate linear regression demonstrated that self-reported religiosity was related to disease stage, asymmetry, and male gender. Results are discussed in the context of other neurologic correlates of religiosity. The pilot study on religious concept activation suggested that the mechanism is organic and hemisphere dependent. On/off drug testing confirmed these findings to be independent of medication effects. Gain/decay semantic modeling suggested that right and left forebrain pathways selectively mediated the time constant of gain and decay, respectively, for religious concepts. CONCLUSION: PD patients exhibit significant differences in both controlled and automatic access to religious concepts with mid/late-stage, male, left-onset patients most impaired in access to religious cognition. The findings indicate that aspects of religious/spiritual cognition appear related to specific cerebral structures.