Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Experimental proof of the electronic charge-transfer mechanism in a YBa<SUB>2</SUB>Cu<SUB>3</SUB>O<SUB>7-x</SUB>-based field-effect transistor

The dynamics of charge transfer in a YBa2Cu3O7-x-based field-effect transistor were studied in the normal state using signal shape analysis and frequency mixing techniques, the latter being the most sensitive means of measuring field effect utilized so far. The speed of response was found to be limited only by the RC time constant of the device configuration (~9 &#181; sec). Also the electric field modulation of the channel resistance was unchanged from dc to the highest frequency achieved in this device, showing the absence of any significant "slow" component. This observation unambiguously demonstrates that direct field induced modulation of the charge carrier density plays a major role in the relatively fast electric field effect in metal-oxide superconductors

Unusual electric field effects in Nd<SUB>0.7</SUB>Sr<SUB>0.3</SUB>MnO<SUB>3</SUB>

Enhanced electric field (E) induced modulation of the resistance of epitaxial thin films of Nd0.7Sr0.3MnO3 has been observed. The results show several remarkable features: first, field-direction-independent decrease of the resistance above the temperature at which the peak in resistivity occurs (Tp); second, proportionality of the modulation to E2; third, a reduction in the magnitude and field-direction-independent reversal of the sign of &#916;R/R just below Tp; and fourth, a prompt time response at high temperatures and a slower response near Tp. These results are consistent with a model of a polarization-induced lattice distortion coupling with both spin and charge transport

Jockey riding racehorse Deputy Ruler onto the racecourse, New South Wales, 1933 [picture].

Title devised from accompanying information where available.; Part of the: Fairfax archive of glass plate negatives.; Fairfax number: .; Also available online at: http://nla.gov.au/nla.pic-vn6265372; Acquired from Fairfax Media, 2012

Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues