A shared neural substrate for action verbs and observed actions in human posterior parietal cortex.

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated that the results are not the product of visual imagery or arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader.

Predicting discharge destination with admission outcome scores in stroke patients.

BACKGROUND: The goal of this study was to predict the discharge location for stroke patients. OBJECTIVE: To design a tool to assess a community discharge that will assist in development of individualized care plans and discharge planning. METHODS: Patients (N = 407) hospitalized for an acute stroke in an inpatient rehabilitation facility were used for this retrospective study. Admission data from the Functional Independence Measure (FIM) and Simplified Stroke Rehabilitation Assessment of Movement (S-STREAM) were used to determine predictive factors for a community discharge. RESULTS: Logistic regressions and chi-square analyses were used to determine admission factors that predict a community discharge and the cut off score for each predictive variable. The S-STREAM, Motor FIM, Total FIM, FIM Bladder, FIM bed transfer, FIM toilet transfer, FIM bathing, and FIM memory were predictive of a community discharge. A predictive tool with a sensitivity and specificity of 76% and 64% was developed using the combined relative risk scores of the S-Stream, FIM Bladder, FIM Bed Transfer and FIM Memory. CONCLUSIONS: By using outcome data at the time of admission, a discharge destination can be predicted for stroke patients with significant sensitivity and specificity.

Women with the Alzheimer's risk marker ApoE4 lose Aß-specific CD4⁺ T cells 10-20 years before men.

Adaptive immunity to self-antigens causes autoimmune disorders, such as multiple sclerosis, psoriasis and type 1 diabetes; paradoxically, T- and B-cell responses to amyloid-ß (Aß) reduce Alzheimer's disease (AD)-associated pathology and cognitive impairment in mouse models of the disease. The manipulation of adaptive immunity has been a promising therapeutic approach for the treatment of AD, although vaccine and anti-Aß antibody approaches have proven difficult in patients, thus far. CD4(+) T cells have a central role in regulating adaptive immune responses to antigens, and Aß-specific CD4(+) T cells have been shown to reduce AD pathology in mouse models. As these cells may facilitate endogenous mechanisms that counter AD, an evaluation of their abundance before and during AD could provide important insights. Aß-CD4see is a new assay developed to quantify Aß-specific CD4(+) T cells in human blood, using dendritic cells derived from human pluripotent stem cells. In tests of >50 human subjects Aß-CD4see showed an age-dependent decline of Aß-specific CD4(+) T cells, which occurs earlier in women than men. In aggregate, men showed a 50% decline in these cells by the age of 70 years, but women reached the same level before the age of 60 years. Notably, women who carried the AD risk marker apolipoproteinE-ɛ4 (ApoE4) showed the earliest decline, with a precipitous drop between 45 and 52 years, when menopause typically begins. Aß-CD4see requires a standard blood draw and provides a minimally invasive approach for assessing changes in Aß biology that may reveal AD-related changes in physiology by a decade. Furthermore, CD4see probes can be modified to target any peptide, providing a powerful new tool to isolate antigen-specific CD4(+) T cells from human subjects.

Biochemical markers in persons with preclinical familial Alzheimer disease.

BACKGROUND: Persons at risk for familial Alzheimer disease (FAD) provide a model in which biomarkers can be studied in presymptomatic disease. METHODS: Twenty-one subjects at risk for presenilin-1 (n = 17) or amyloid precursor protein (n = 4) mutations underwent evaluation with the Clinical Dementia Rating (CDR) scale. We obtained plasma from all subjects and CSF from 11. Plasma (Abeta(40), Abeta(42), F(2)-isoprostanes) and CSF (F(2)-isoprostanes, t-tau, p-tau(181), Abeta(40), Abeta(42), and Abeta(42)/Abeta(40) ratio) levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs). RESULTS: Plasma Abeta(42) levels (25.1 pM vs 15.5 pM, p = 0.031) and the ratio of Abeta(42)/Abeta(40) (0.16 vs 0.11, p = 0.045) were higher in presymptomatic MCs. Among MCs, those with CDR scores of 0.5 had lower plasma Abeta(42) levels than those with CDR scores of 0 (14.1 pM vs 25.1, p = 0.02). The ratio of Abeta(42) to Abeta(40) was also reduced in the CSF (0.08 vs 0.15, p = 0.046) of nondemented MCs compared to NCs. Total CSF tau and p-tau(181) levels were elevated in presymptomatic FAD MCs. CSF levels of F(2)-isoprostanes were also elevated in MCs (n = 7, 48.6 pg/mL) compared to NCs (n = 4, 21.6 pg/mL, p = 0.031). CONCLUSIONS: Our data indicate that Abeta(42) is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta(42) to Abeta(40) was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau(181) are sensitive indicators of presymptomatic disease. Our finding of elevated F(2)-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.

Regionally specific modulation of brain apolipoprotein E in the mouse during the estrous cycle and by exogenous 17beta estradiol.

Studies have suggested that 17beta estradiol (E2) can modify apolipoprotein E (apoE) expression. The current study determined if apoE protein varied in different regions of the mouse brain as a function of the estrous cycle and if E2 could increase apoE protein expression. In this study apoE concentration was lowest on estrus in the hippocampus, cingulate cortex and frontal cortex. In contrast, apoE concentration was highest on estrus in the olfactory bulb and cerebellum. There were no differences in the striatal apoE expression throughout the estrous cycle. Exogenous E2 significantly raised tissue levels of apoE in the olfactory bulb and cerebellum at 5 days after treatment. There was a slight, but nonsignificant increase in cortical expression of apoE and no change in striatum. Immunocytochemical localization studies found estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) in cortical neurons and glia. In the cerebellum and olfactory bulb, ERbeta was seen primarily in glia. ERalpha was not observed in the cerebellum and was rare in the olfactory bulb. Neither ERalpha nor ERbeta was seen in the striatum. Our data show regional differences in the production of apoE throughout the estrous cycle. In addition, exogenous E2 has regionally specific effects on apoE expression. Regional variability in apoE production appears to vary as a function of the estrogen receptor subtype.