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A number of distinct [beta]-amyloid (A[beta]) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural A[beta]-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic A[beta] and amyloidogenic non-A[beta] species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21-89 years. Antibody reactivity was most prominent against oligomeric assemblies of A[beta] and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of A[beta]1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant A[beta], ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from A[beta] toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with A[beta] the monkeys developed high titers not only against A[beta] peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of A[beta] antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.

Spatial structure in metacommunities and their relationships to environmental gradients have been linked to opposing theories of community assembly. In particular, while the species sorting hypothesis predicts strong environmental influences, the neutral theory, the mass effect, and the patch dynamics frameworks all predict differing degrees of spatial structure resulting from dispersal and competition limitations. Here we study the relative influence of environmental gradients and spatial structure in bird assemblages of the Chilean temperate forest. We carried out bird and vegetation surveys in South American temperate forests at 147 points located in nine different protected areas in central Chile, and collected meteorological and productivity data for these localities. Species composition dissimilarities between sites were calculated, as well as three indices of bird local diversity: observed species richness, Chao estimate of richness, and Shannon diversity. A stepwise multiple regression and partial regression analyses were used to select a small number of environmental factors that predicted bird species diversity. Although diversity indices were spatially autocorrelated, environmental factors were sufficient to account for this autocorrelation. Moreover, community dissimilarities were not significantly related to distance between sites. We then tested a multivariate hypothesis about climate, vegetation, and avian diversity interactions using a structural equation modeling (SEM) approach. The SEM showed that climate and area of fragments have important indirect effects on avian diversity, mediated through changes in vegetation structure. Given the scale of this study, the metacommunity framework provides useful insights into the mechanisms driving bird assemblages in this region. Taken together, the weak spatial structure of community composition and diversity, as well as the strong environmental effects on bird diversity, support the interpretation that species sorting has a predominant role in structuring avian assemblages in the region. Key words: area effect; dissimilarity; diversity; metacommunity; Patagonia; richness; species sorting; temperate forest; turnover rates; vegetation structure.