Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection.

Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques and intracellular tau neurofibrillary tangles in Alzheimer's disease (AD). In addition, AD is characterized by an increase in astrocyte reactivity. The chaperone HSPB1 has been proposed as a marker for reactive astrocytes; however, its astrocytic functions in neurodegeneration remain to be elucidated. Here, we identify that HSPB1 is secreted from astrocytes to exert non-cell-autonomous protective functions. We show that in human AD brain, HSPB1 levels increase in astrocytes that cluster around amyloid plaques, as well as in the adjacent extracellular space. Moreover, in conditions that mimic an inflammatory reactive response, astrocytes increase HSPB1 secretion. Concomitantly, astrocytes and neurons can uptake astrocyte-secreted HSPB1, which is accompanied by an attenuation of the inflammatory response in reactive astrocytes and reduced pathological tau inclusions. Our findings highlight a protective mechanism in disease conditions that encompasses the secretion of a chaperone typically regarded as intracellular.

Trends, patterns, and factors associated with HIV infection among males diagnosed with syphilis, 2014-2019, Hawaii.

OBJECTIVE: This study describes HIV infection and associated risk factors among males diagnosed with syphilis in Hawaii. METHODS: Hawaii sexually transmitted infection (STI) registry records of males diagnosed with syphilis, 2014-2019, were crossmatched with Hawaii HIV surveillance registry records through 2020 using CDC's Registry Plus Link Plus software. HIV status from the STI registry was validated by matching results. Logistic regression was used to examine demographic and behavioral factors associated with HIV infection. RESULTS: Among the 947 male syphilis cases, 257 (27.1%) had both syphilis and HIV infections. Dual infection rates were higher in earlier years (39.5% in 2015), among older patients (41.6% among persons ≥45 years old), males who have sex with males (MSM, 36.6%), and cases with repeated syphilis events (59.5%). The overall agreement on HIV status between the STI registry and matching results was 95.7%. CONCLUSIONS: Over a quarter (27.1%) of male syphilis cases were living with HIV. HIV infection rates were higher among older patients, MSM, and males with repeated syphilis events. Periodic matching between STI and HIV registries provides opportunities for quality control to both registries and opportunities to identify patients not linked to HIV care or who have fallen out of HIV care.

Autophagy in Astrocytes and its Implications in Neurodegeneration.

Autophagy is a major degradation pathway where double-membrane vesicles called autophagosomes deliver cytoplasmic content to the lysosome. Increasing evidence suggests that autophagy dysfunction contributes to the pathogenesis of neurodegenerative diseases. In addition, misfolded proteins that accumulate in these diseases and constitute a common pathological hallmark are substrates for autophagic degradation. Astrocytes, a major type of glial cells, are emerging as a critical component in most neurodegenerative diseases. This review will summarize the recent efforts to investigate the role that autophagy plays in astrocytes in the context of neurodegenerative diseases. While the field has mostly focused on the implications of autophagy in neurons, autophagy may also be involved in the clearance of disease-related proteins in astrocytes as well as in maintaining astrocyte function, which could impact the cell autonomous and non-cell autonomous contribution of astrocytes to neurodegeneration.

Imbalance in the response of pre- and post-synaptic components to amyloidopathy.

Alzheimer's disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Amyloid ß (Aß) species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functional impairments observed in AD. It is, however, still unclear how Aß plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that Aß plaques grow faster in the earlier stages of the disease and if their initial area is >500 µm2; this may be due to deposition occurring in the outer regions of the plaque, the plaque cloud. In addition, synaptic turnover is higher in the presence of amyloid pathology and this is paralleled by a reduction in pre- but not post-synaptic densities. Plaque proximity does not appear to have an impact on synaptic dynamics. These observations indicate an imbalance in the response of the pre- and post-synaptic terminals and that therapeutics, alongside targeting the underlying pathology, need to address changes in synapse dynamics.