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Posters: P-106 P-106

GENDER, AGE, AND APOE GENOTYPE EFFECTS ON CSF A␤42 IN COGNITIVELY NORMAL ADULTS

Elaine R. Peskind1, Gail Li1, Eric C. Petrie1, James B. Leverenz1, Murray A. Raskind1, Douglas Galasko2, 1VA Puget Sound Health Care System, MIRECC, Seattle, WA, USA; 2University of California, San Diego, San Diego, CA, USA. Contact e-mail: [email protected] Background: Neurodegenerative changes of Alzheimer’s disease (AD) may begin many years prior to clinical manifestations, and women have an increased risk of AD compared to men. We recently showed that CSF levels of A␤42, a sensitive AD biomarker, are significantly lower in cognitively normal apolipoprotein E*4 (APOE*E) allele carriers vs. noncarriers starting as early as 50-60 years of age. Objective: Here we examined gender effects on this relationship. Methods: Subjects were 184 cognitively normal persons aged 21-88. CSF A␤42 was measured by sandwich ELISA. APOE genotype was determined. The relationship among A␤42, age, gender and APOE genotype was examined using a linear regression model. Age was modeled as an orthogonal quadratic polynomial to separate our linear from quadratic trends in the A␤42-age relationship. Results: Among APOE*4 allele carriers, CSF A␤42 levels in women remained stable until the early postmenopausal period (age 55-60) and then declined sharply, while in male APOE*4 allele carriers, CSFA␤42 levels declined linearly from age 21 (age X gender interaction p ⫽ 0.007), with the relationship between age and A␤42 being mainly negative and linear for men, but quadratic for women. In APOE*4 negative subjects, the A␤42-age curve was not significantly different between genders—there was no significant interaction between age and gender (p ⫽ 0.2) and no difference in mean A␤42 levels between genders (p ⫽ 0.2). Conclusions: Preclinical neuropathologic changes associated with AD may begin later (after menopause) in women compared to men, suggesting a possible protective effect of estrogen against A␤42 deposition in women. P-107

NEUROINFLAMMATION AND NEURONAL NETWORKS ACTIVATION INVOLVED IN LEARNING AND MEMORY

Susanna Rosi1, Heather L. Milliken1, Victor Ramirez-Amaya2, Almira Varzdarjanova3, Paul Worley4, Carol Barnes5, 1Brain and Spinal Cord Injury Center, University of California San Francisco, San Francisco, CA, USA; 2Instit Fisiol Cel, UNAM, Queretaro, Mexico; 3 Medical College of Georgia, Augusta, GA, USA; 4Neurosci & Neurol, John Hopkins Univ, Baltimore, MD, USA; 5Neural Systems memory and Aging, University of Arizona, Tucson, AZ, USA. Contact e-mail: [email protected] Neuroinflammation is associated with a variety of neurological diseases, such as Alzheimer disease (AD), and is reliably detected by the presence of activated microglia. In early AD, high numbers of activated microglia are observed, particularly in brain regions involved in memory (e.g. hippocampus, entorhinal cortex). The ability of neurons to alter their transcriptional programs in response to synaptic input, also known as synaptic plasticity, is of fundamental importance to the mechanisms underlying learning and memory. Previously, we showed that neuroinflammation, induced by chronic lipopolysaccaride-infusion in young rats, led to a significant increase in the number of neurons expressing the behaviorallyinduced immediate early gene Arc in hippocampal regions that showed activated microglia. Arc is transcribed in neurons that are part of stable neural networks activated during spatial exploratory behaviors. Given the role of Arc regulation in synaptic plasticity and memory, we hypothesized that neuroinflammation alters synaptic activity associated with spatial learning and memory. To test this hypothesis, we exposed rodents to 2 distinct learning experiences separated by a rest interval. Using a novel and sensitive technique, cellular compartmental analysis of temporal activity by fluorescence in situ hybridization (catFISH), we could assess the activity history of neurons in the CA1 area and entorhinal cortex. Here we found

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that Arc mRNA expression was induced in the same group neurons after exploration of the same novel environment while two different populations of neurons responded to two different environments in animals with experimental induced inflammation, similar to the control animals. Our data suggest that the CA1 area of the hippocampus is able to compensate for the neuroinflammation-induced alteration of activity in the DG and CA3 areas, perhaps through the direct projection from the layer III entorhinal cortical input to CA1. We are currently identifying the temporal dynamics of Arc transcription and Arc protein translation in the different layers of the entorhinal cortex and as it relates to the extent of microglial activation. Understanding how the presence of activated microglia affects synaptic plasticity is of critical importance for the development of strategies to prevent cognitive dysfunctions associated with initial stages of AD. P-108

CREATION AND VALIDATION OF AN ALZHEIMER’S QUESTIONNAIRE

Christine M. Belden, Marwan N. Sabbagh, Donald J. Connor, Sun Health Research Institute, Sun City, AZ, USA. Contact e-mail: [email protected] Background: Confidence in making a diagnosis of AD remains elusive. This stems from the NINCDS-ADRDA criteria which state that a definitive diagnosis of AD can only be established by biopsy or autopsy. Furthermore, evidence strongly suggests that physicians, bombarded by demands for care amidst increasing number of medical conditions are not sufficiently sensitive to signs of cognitive impairment or early dementia. Many physicians do not screen for cognitive problems in their practices unless they receive complaints from either patients or patients’ families. Consequently, recognition of dementia by primary care physicians is poor until it is at least moderately advanced. It is estimated that at least 50% of cases of mild to moderate dementia are missed. Delaying diagnosis results in an increased likelihood of disease progression before intervention is attempted. Providers cite a lack of confidence in diagnosing AD as a primary reason that half of all AD patients remain undiagnosed. Screening has been proposed to help combat under-diagnosis but validated, structured, interview based instruments are lacking. Objective: To create and validate an AD screening questionnaire with reasonable sensitivity to detect changes in cognitive functioning. Methods: We have developed the Alzheimer’s Questionnaire (AQ), a clinician-administered and informant-based screening instrument. Weighted scores are based upon our impressions of importance with regard to history gathering. We administered the AQ to informants for 17 subjects with probable AD based upon NINDS-ADRDA criteria (mean age 80.2 ⫾ 5.1 years, 14.0⫾ 3.1 years education, mean MMSE 20.6⫾6.8, mean AQ 20.6⫾4.3) and 8 NC subjects (mean age 76.6 ⫾ 3.6 years, 16.6⫾ 2.4 years education, mean MMSE 29.9⫾0.3, mean AQ 0.4⫾0.5). Results: When the cut point is set at 7, the AQ discriminates NC from AD with 100% sensitivity and 100% specificity. The mean time to administer the AQ is 2.6 ⫾ 0.6 minutes and the mean AQ score differed significantly between NC and AD (p⬍0.0001). Conclusions: The AQ is a sensitive measure for detecting AD and can be used in a primary care setting as a structured interview technique for ascertainment of cognitive complaints. Differential diagnosis between dementia subtypes and further validation remain to be elucidated. P-109

SUBCLINICAL HYPERPARATHYROIDISM, AN AGE DEPENDENT PHENOMENA, IS AN ANTECEDENT OF BOTH OSTEOPOROSIS AND DEMENTIA

Eric R. Braverman1, Vanessa Arcuri1, Kenneth Blum1,2. 1Path Foundation, NY, NY, USA; 2Wake Forest University, Winston-Salem, NC, USA. Contact e-mail: [email protected] Parathyroid glands cause bones to release calcium, over time this weakens bone density and leads to osteoporosis (OP). Hyperparathyroidism is blood level of PTH above 70 pg/ml. Kidney disease studies suggest that PTH