In vivo tau pathology is associated with synaptic loss and altered synaptic function

BACKGROUND: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([{18}^F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. METHODS: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-minV [{18}^F]flortaucipir PET, dynamic 60-min [{11}^C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [{18^}F]flortaucipir- and [{11}^C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [{18}^F]flortaucipir BPND, [{11}^C]UCB-J BP_{ND} and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. RESULTS: Across subjects, higher regional [{18}^F]flortaucipir uptake was associated with lower [{11}^C]UCB-J uptake. Within subjects, the association between [{11}^C]UCB-J and [{18}^F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [{18}^F]flortaucipir and lower [{11}^C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. CONCLUSIONS: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction

Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems

Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii

Aberrant Neuronal Dynamics during Working Memory Operations in the Aging HIV-Infected Brain

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were significantly less accurate on the working memory task and their neuronal dynamics indicated that encoding operations were preserved, while memory maintenance processes were abnormal. Specifically, no group differences were detected during the encoding period, yet dysfunction in occipital, fronto-temporal, hippocampal, and cerebellar cortices emerged during memory maintenance. In addition, task performance in the controls covaried with occipital alpha synchronization and activity in right prefrontal cortices. In conclusion, working memory impairments are common and significantly impact the daily functioning and independence of HIV-infected patients. These impairments likely reflect deficits in the maintenance of memory representations, not failures to adequately encode stimuli