Alzheimer's Disease & Dementia

Wednesday 14 May 2014

Michael Zeineh¹, Hannes Vogel², Yuanxin Chen³, Hagen Kitzler⁴, Scott Atlas², and Brian Rutt^2
1Radiology, Stanford University, Stanford, CA, United States, ²Stanford University, Stanford, California, United States, ³Robarts Research Institute, Ontario, Canada, ⁴Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Germany

Hypointense foci in the medial temporal lobe may reflect Alzheimer’s pathology. To discern the etiology of iron accumulation in Alzheimer’s disease, we performed high-resolution GRE imaging at 7.0T of AD specimens. We registered and evaluated concurrent DAB-iron, CD163-microglia, and beta-amyloid stains of the same specimens. Iron containing foci best explained the MR hypointense foci that accumulated at and along the undersurface of the CA1/subiculum junction. This iron was primarily localized within microglia, not amyloid plaques.

Aikaterini Kotrotsou¹, David A. Bennett², Julie A. Schneider², Sue E. Leurgans², Tom Golak¹, and Konstantinos Arfanakis^1,2
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States

Brain atrophy is considered a biomarker of Alzheimer's disease (AD) pathology. However, mixed pathologies are common in the elderly, and several of them may lead to atrophy. Also, only a handful of studies with low numbers of participants have combined brain MR volumetry with measures of neuropathology obtained after death. Thus, the relation between brain atrophy and age-related neuropathology is actually not well-established. The purpose of this investigation was to assess the neuropathologic correlates of regional brain volumes by combining ex-vivo MR volumetry and pathology information on a large community cohort of older persons.

Lirong Yan¹, Collin Liu², Koon-Pong Wong¹, Sung-Cheng Huang¹, David Wharton¹, John Ringman^1,3, and Danny JJ Wang^1
1University of California Los Angeles, Los Angeles, CA, United States, ²University of South California, CA, United States, ³Mary S. Easton Center for Alzheimer's Disease Research, University of California Los Angeles, CA, United States

The purpose of this study is to investigate the relationship between pseudo-continuous ASL (pCASL) perfusion and the parameters of relative perfusion (R1) and tracer distribution volume ratio (DVR) derived from PiB-PET in 25 familial Alzheimer¡¯s disease related subjects. The spatial patterns between pCASL CBF and PiB-PET R1 are highly consistent with significant voxel-wise correlations, whereas the correlation between pCASL perfusion and PiB-PET DVR is negative across subjects. Our study supports the validity of both pCASL and PiB-PET as imaging markers of Alzheimer¡¯s disease.

Megha M Vasavada¹, Han Zhang², Jianli Wang¹, Prasanna Karunanayaka¹, Paul Eslinger³, David Gill⁴, Bing Zhang⁵, and Qing X Yang^1
1Radiology, Pennsylvania State College of Medicine, Hershey, PA, United States, ²Hangzhou Normal University, Hangzhou, Zhejiang, China, ³Neurology, Pennsylvania State College of Medicine, PA, United States, ⁴Unity Rehabilitation and Neurology at Ridgeway, NY, United States, ⁵Radiology, Nanjing university medical school, Nanjing, China

Olfactory deficits are known to occur in patients with mild cognitive impairment (MCI) and early Alzheimer’s disease. In this work, we performed olfactory functional magnetic resonance imaging of the primary olfactory cortex and demonstrated that the primary olfactory cortex is involved functionally in early Alzheimer’s disease.

Valerio Zerbi^1,2, Maximilian Wiesmann³, Diane Jansen¹, Laus M Broersen⁴, Christian F Beckmann⁵, Arend Heerschap², and Amanda J Kiliaan^1
1Anatomy, Donders Institute for Brain Cognition & Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ³Geriatric Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands,⁴Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, Netherlands, ⁵MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Netherlands

A specific combination of omega-3 fatty acids with precursors and cofactors in membrane synthesis was developed for the dietary management of AD, specifically to enhance the formation of neuronal membranes and synapses. In this study, we tested the hypothesis that a specific multi-nutrient diet is able to positively influence brain connectivity and vascular health in a mouse model for AD vascular risk factor (apoE4). Resting state functional MRI and cerebral blood flow were assessed by MRI at 11.7T. Results showed enhanced perfusion, increased neural connectivity; and increased number of post-synapses in animals fed with a multi-nutrient diet.

Ai-Ling Lin^1,2, Wei Zhang¹, and Arlan Richardson^2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Cellular & Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

In the study, we used multi-metric MRI methods to evaluate the treatment efficacy of rapamycin on cerebrovascular functions in mice expressing the human e4 allele of the apolipoprotein E gene (APOE4), which is a risk factor for Alzheimer’s disease (AD). We found that young APOE4 mice treated with rapamycin had significantly restored cerebral blood flow and blood brain barrier integrity compared to the non-treated group, and the effects were prominent over time. The restored cerebrovascular functions in the APOE4 mice resembled those of age-matched wild-type mice. Our results suggest that rapamycin would be promising for future treatment/prevention of AD.

Rachelle Crescenzi^1,2, Catherine DeBrosse^1,2, Ravi Prakash Reddy Nanga², Hari Hariharan², Ari Borthakur², John Detre³, Virginia M.-Y. Lee⁴, and Ravinder Reddy^2
1Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, United States, ²Center for Magnetic Resonance and Optical Imaging (CMROI), University of Pennsylvania, Philadelphia, PA, United States, ³Center for Functional Neuroimaging (CfN), University of Pennsylvania, Philadelphia, PA, United States, ⁴Center for Neurodegenerative Disease Research (CNDR), University of Pennsylvania, Philadelphia, PA, United States

Synapse loss is the main correlate of cognitive defecits in AD. Here, synapse loss in the sub-regions of the hippocampus of the P301S tauopathic mouse brain is shown to correlate with glutamate loss measured by GluCEST: glutamate chemical exchange saturation transfer. Average GluCEST is decreased in the thalamus/hypo-thalamus and CA sub-region of the hippocampus, yet maintained in the dentate gyrus. Immunohistochemistry confirms that synapse loss occurs throughout the transgenic brain, except in the DG where neurons are known to be regenerated. GluCEST imaging allows the DG neuronal integrity to be observed in vivo, which was not possible using conventional spectroscopy.

Kristof Govaerts¹, Uwe Himmelreich¹, Fred Van Leuven², and Tom Dresselaers^1
1Imaging & Pathology, KU Leuven, Leuven, Vlaams-Brabant, Belgium, ²Human Genetics, KU Leuven, Leuven, Vlaams-Brabant, Belgium

Tempoparietal hypoperfusion is an early symptom of Alzheimer’s Disease (AD). Recent studies in AD and mild cognitive impairment (MCI) patients also suggest that the cerebrovascular response to hypercapnia (CVR) may be a more sensitive readout. We performed arterial spin labeling to determine cerebral blood flow increases in response to a hypoventilation-induced hypercapnic challenge in a bigenic biAT mice, a model for AD. We report decreased basal perfusion already at young age (3 months), as well as a significantly increased CVR in response to hypoventilation-induced hypercapnia.

Matthias Vandesquille^1,2, Tengfei Li^2,3, Chrystelle Po¹, Christelle Ganneau², Christian Czech⁴, Charles Duyckaerts³, Benoît Delatour³, Sylvie Bay², Pierre Lafaye², and Marc Dhenain^1
1MIRCen, CEA, Fontenay-aux-Roses, France, ²Institut Pasteur, Paris, France, ³ICM, Hôpital de la Pitié-Salpêtrière, Paris, France, ⁴Hoffmann-La Roche, Basel, Switzerland

Amyloid deposits occur many years before neuropsychological symptoms of Alzheimer's disease. Their detection by MRI is thus critical. We designed a contrast agent combining the properties of VHH antibodies and gadolinium to specifically label amyloid plaques by MRI. We showed that hypointense spots were observed on T2* images following in vitro incubation or in vivo ICV injection of the VHH-DOTA/Gd. Several spots were colocalized with the amyloid plaques revealed by a reference (Gold-standard) Gd-staining procedure. Overall, this study describes a new promising tool for the detection of amyloid deposits by MRI.

Pablo Garcia-Polo^1,2, Virginia Mato^1,3, Daniel Garcia-Frank^1,4, Norberto Malpica¹, Juan Alvarez-Linera⁵, and Juan Antonio Hernandez-Tamames^2,3
1LAIMBIO-DTE, Universidad Rey Juan Carlos, Mostoles, Madrid, Spain, ²Center for Biomedical Technology U.P.M., Pozuelo de Alarcon, Madrid, Spain,³Center for Alzheimer's Disease Queen Sofia Foundation CIEN Foundation, Madrid, Madrid, Spain, ⁴IdiPAZ, Madrid, Spain, ⁵Hospital Ruber Internacional, Madrid, Spain

This work analyses structural and physiological features in a healthy population (25 subjects, PAD group) in risk of developing Alzheimer's disease (left and right hippocampus mean-2std.) the asl technique provides perfusion maps that, after normalization and partial volume effect correction steps, are studied through a two-sample t-test (25 subjects control group). also, segmented 3dt1w images with vbm-dartel. pad, as expected, suffer from grey matter loss in both hippocampi and, additionally, hypoperfusion hippocampi, amygdala entorhinal cortex. we propose to include studies, more sensitive than structural vbm, standard research criteria for early diagnosis of ad.