CSF sTREM2: Marking the tipping point between preclinical AD and dementia?

Biomarkers for Alzheimer's disease (AD) have improved our understanding of the temporal sequence of biological events that lead to AD dementia (Jack et al, 2013). AD is characterized neuropathologically by amyloid plaques comprised of the amyloid‐β peptide and neurofibrillary tangles comprised of tau. Brain amyloid deposition, as evidenced by a decline in amyloid‐β peptide 42 (Aβ42) in the cerebrospinal fluid (CSF) or by binding of amyloid PET ligands, is thought to be a key initiating event in AD and begins many years prior to the onset of dementia. A rise in CSF tau and phosphorylated tau in the setting of Aβ deposition appears to reflect neurodegeneration and also begins years prior to the onset of dementia but after Aβ deposition has begun to accumulate. Individuals with “preclinical AD,” that is, normal cognition but abnormal AD biomarkers, have a much higher risk for developing AD dementia but may remain cognitively normal for years (Vos et al, 2013). While deposition of amyloid and formation of tau tangles are necessary for AD to occur, it is likely that additional events involving inflammation or other processes contribute to crossing the tipping point from preclinical AD to AD dementia. Current efforts are aimed at defining the biomarker(s) that best predict the transition from cognitive normality to abnormality. A biomarker that is closely associated with the onset of cognitive decline could help us to understand the biological events that connect amyloid deposition and tangle formation to cognitive decline and could have significant practical value in AD diagnosis and clinical trial design

On the Estimation of Systematic Uncertainties of Star Formation Histories

In most star formation history (SFH) measurements, the reported uncertainties are those due to effects whose sizes can be readily measured: Poisson noise, adopted distance and extinction, and binning choices in the solution itself. However, the largest source of error, systematics in the adopted isochrones, is usually ignored and very rarely explicitly incorporated into the uncertainties. I propose a process by which estimates of the uncertainties due to evolutionary models can be incorporated into the SFH uncertainties. This process relies on application of shifts in temperature and luminosity, the sizes of which must be calibrated for the data being analyzed. While there are inherent limitations, the ability to estimate the effect of systematic errors and include them in the overall uncertainty is significant. Effects of this are most notable in the case of shallow photometry, with which SFH measurements rely on evolved stars.Comment: 28 pages, 9 figures, ApJ in pres

Altered sleep and EEG power in the P301S Tau transgenic mouse model

OBJECTIVE: Sleep disturbances are prevalent in human tauopathies yet despite the importance of sleep, little is known about its relationship with tau pathology. Here, we investigate this interaction by analyzing sleep and tau pathology throughout tauopathy disease progression in P301S human tau transgenic mice. METHODS: P301S and wild‐type mice were analyzed by electroencephalography (EEG)/electromyography at 3, 6, 9, and 11 months of age for sleep/wake time, EEG power, and homeostatic response. Cortical volume and tau pathology was also assessed by anti‐phospho‐tau AT8 staining. RESULTS: P301S tau mice had significantly decreased rapid eye movement (REM) sleep at 9 months of age and decreased REM and non‐REM (NREM) sleep as well as increased wakefulness at 11 months. Sleep loss was characterized by fewer wake, REM, and NREM bouts, increased wake bout duration, and decreased sleep bout duration. Decreased REM and NREM sleep was associated with increased brainstem tau pathology in the sublaterodorsal area and parafacial zone, respectively. P301S mice also showed increased EEG power at 6 and 9 months of age and decreased power at 11 months. Decreased EEG power was associated with decreased cortical volume. Despite sleep disturbances, P301S mice maintained homeostatic response to sleep deprivation. INTERPRETATION: Our results indicate that tau pathology is associated with sleep disturbances that worsen with age and these changes may be related to tau pathology in brainstem sleep regulating regions as well as neurodegeneration. Tau‐induced sleep changes could affect disease progression and be a marker for therapeutic efficacy in this and other tauopathy models

Stellar Populations in the Phoenix Dwarf (dIrr/dSph) Galaxy as Observed by HST/WFPC2

We present HST/WFPC2 photometry of the central regions of the Phoenix dwarf. Accurate photometry allows us to: 1) confirm the existence of the horizontal branch previously detected by ground-based observations, and use it to determine a distance to Phoenix, 2) clearly detect the existence of multiple ages in the stellar population of Phoenix, 3) determine a mean metallicity of the old red giant branch stars in Phoenix, and suggest that Phoenix has evolved chemically over its lifetime, 4) extract a rough star formation history for the central regions which suggests that Phoenix has been forming stars roughly continuously over its entire lifetime.Comment: Accepted by AJ, 22 pages including 6 figures + 1 figure in JPEG forma

Gas Seepage and Pockmark Formation From Subsurface Reservoirs:Insights From Table-Top Experiments

Pockmarks are morphological depressions commonly observed in ocean and lake floors. Pockmarks form by fluid (typically gas) seepage thorough a sealing sedimentary layer, deforming and breaching the layer. The seepage-induced sediment deformation mechanisms, and their links to the resulting pockmarks morphology, are not well understood. To bridge this gap, we conduct laboratory experiments in which gas seeps through a granular (sand) reservoir, overlaid by a (clay) seal, both submerged under water. We find that gas rises through the reservoir and accumulates at the seal base. Once sufficient gas over-pressure is achieved, gas deforms the seal, and finally escapes via either: (a) doming of the seal followed by dome breaching via fracturing; (b) brittle faulting, delineating a plug, which is lifted by the gas seeping through the bounding faults; or (c) plastic deformation by bubbles ascending through the seal. The preferred mechanism is found to depend on the seal thickness and stiffness: in stiff seals, a transition from doming and fracturing to brittle faulting occurs as the thickness increases, whereas bubble rise is preferred in the most compliant, thickest seals. Seepage can also occur by mixed modes, such as bubbles rising in faults. Repeated seepage events suspend the sediment at the surface and create pockmarks. We present a quantitative analysis that explains the tendency for the various modes of deformation observed experimentally. Finally, we connect simple theoretical arguments with field observations, highlighting similarities and differences that bound the applicability of laboratory experiments to natural pockmarks.</p

Comparing the Ancient Star Formation Histories of the Magellanic Clouds

We present preliminary results from a new HST archival program aimed at tightly constraining the ancient (>4 Gyr ago) star formation histories (SFHs) of the field populations of the SMC and LMC. We demonstrate the quality of the archival data by constructing HST/WFPC2-based color-magnitude diagrams (CMDs; M_{F555W} ~ +8) for 7 spatially diverse fields in the SMC and 8 fields in the LMC. The HST-based CMDs are >2 magnitudes deeper than any from ground based observations, and are particularly superior in high surface brightness regions, e.g., the LMC bar, which contain a significant fraction of star formation and are crowding limited from ground based observations. To minimize systematic uncertainties, we derive the SFH of each field using an identical maximum likelihood CMD fitting technique. We then compute an approximate mass weighted average SFH for each galaxy. We find that both galaxies lack a dominant burst of early star formation, which suggests either a suppression or an under-fueling of early star formation. From 10-12 Gyr ago, the LMC experienced a period of enhanced stellar mass growth relative to the SMC. Similar to some previous studies, we find two notable peaks in the SFH of the SMC at ~4.5 and 9 Gyr ago, which could be due to repeated close passages with the LMC, implying an interaction history that has persisted for at least 9 Gyr. We find little evidence for strong periodic behavior in the lifetime SFHs of both MCs, suggesting that repeated encounters with the Milky Way are unlikely. Beginning ~3.5 Gyr ago, both galaxies show increases in their SFHs, in agreement with previous studies, and thereafter, track each other remarkably well. (abridged)Comment: 9 pages, 5 Figures, Accepted for Publication in MNRA

The age-metallicity relationship of the Large Magellanic Cloud field star population from wide-field Washington photometry

We analyze ages and metallicities for some 5.5 million stars distributed throughout the Large Magellanic Cloud (LMC) main body, obtained from CCD Washington CT1 photometry. We produce a comprehensive field star Age-Metallicity Relationship (AMR) from the earliest epoch until ~1 Gyr ago. This AMR reveals that the LMC has not evolved chemically as either a closed-box or bursting system, exclusively, but as a combination of both scenarios that have varied in relative strength over the lifetime of the galaxy, although the bursting model falls closer to the data in general. Furthermore, while old and metal-poor field stars have been preferentially formed in the outer disk, younger and more metal-rich stars have mostly been formed in the inner disk, confirming an outside-in formation. We provide evidence for the formation of stars between 5 and 12 Gyr, during the cluster age gap, although chemical enrichment during this period was minimal. We find no significant metallicity gradient in the LMC. We also find that the range in the metallicity of an LMC field has varied during the lifetime of the LMC. In particular, we find only a small range of the metal abundance in the outer disk fields, whereas an average range of Delta([Fe/H]) = +0.3\pm0.1 dex appears in the inner disk fields.Comment: The Astronomical Journal, accepte