Sarinporn Manitsirikul

Association between apolipoprotein a-i levels and white matter hyperintensities depends on CSF tau levels in a high-risk cohort of aging cognitively normal persons: The prevent-alzheimer's disease study

Values Nelly Joseph-Mathurin, Yi Su, Andrei Vlassenko, Lars Couture, Tyler Blazey, Karl A. Friedrichsen, Christopher J. Owen, Russ C. Hornbeck, Lisa Cash, Trish A. Stevenson, Beau Ances, Chengjie Xiong, Virginia Buckles, Krista L. Moulder, John C. Morris, Randall Bateman, Marcus E. Raichle, Tammie L. S. Benzinger,Washington University School ofMedicine, St Louis, MO, USA. Contact e-mail: mathurinn@npg.wustl.edu

How to follow up and cluster subjects by longitudinal changes of fibrillary amyloid imaging and CSF biomarkers? a 24-month follow up

Figure 1. Vertex-based multivariate linear regression model showing the effect of amyloid load on the rate of hypo-metabolism in each disease stage, corrected for baseline glucose metabolism, age, gender and apoe genotype. Only LMCI and AD stages show positive effect from amyloid load on hypometabolism in temporo-parietal and precuneus regions. Sulantha S. Mathotaarachchi, Sara Mohades, Monica Shin, Thomas Beaudry, Andrea Lessa Benedet, Tharick Ali Pascoal, Seqian Wang, Sarinporn Manitsirikul, Maxime J. Parent, Min Su Kang, Vladimir Fonov, Chang Oh Chung, Sr., Serge Gauthier, Pedro RosaNeto, McGill University, Montreal, QC, Canada; McGill Centre for Studies in Aging, Montreal, QC, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, QC, Canada; McGill Centre for Studies in Aging, Verdun, QC, Canada; McGill University Centre for Studies in Aging, Verdun, QC, Canada; Image Processing Laboratory, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Centre for Studies on Prevention of Alzheimer’s Disease (StoP-AD Centre), Douglas Mental Health Institute, Montreal, QC, Canada; Douglas Hospital Research Centre, Montreal, QC, Canada; Translational Imaging Laboratory, Montreal, QC, Canada. Contact e-mail: sulantha.s@gmail.com

Should a global or a regional measure of amyloidosis be used in a longitudinal study

Figure 1. Vertex-based multivariate linear regression model showing the effect of amyloid load on the rate of hypo-metabolism in each disease stage, corrected for baseline glucose metabolism, age, gender and apoe genotype. Only LMCI and AD stages show positive effect from amyloid load on hypometabolism in temporo-parietal and precuneus regions. Sulantha S. Mathotaarachchi, Sara Mohades, Monica Shin, Thomas Beaudry, Andrea Lessa Benedet, Tharick Ali Pascoal, Seqian Wang, Sarinporn Manitsirikul, Maxime J. Parent, Min Su Kang, Vladimir Fonov, Chang Oh Chung, Sr., Serge Gauthier, Pedro RosaNeto, McGill University, Montreal, QC, Canada; McGill Centre for Studies in Aging, Montreal, QC, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, QC, Canada; McGill Centre for Studies in Aging, Verdun, QC, Canada; McGill University Centre for Studies in Aging, Verdun, QC, Canada; Image Processing Laboratory, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Centre for Studies on Prevention of Alzheimer’s Disease (StoP-AD Centre), Douglas Mental Health Institute, Montreal, QC, Canada; Douglas Hospital Research Centre, Montreal, QC, Canada; Translational Imaging Laboratory, Montreal, QC, Canada. Contact e-mail: sulantha.s@gmail.com

Genome-wide association study in PET imaging longitudinal data

Background: Early onset Alzheimer’s disease (AD) occurs under 65 years of age, which represents a minority in all AD cases. Three main causative genes for EOAD were identified: APP, PSEN1 and PSEN2, for their genetic patho-mechanisms by cloning them into mammalian cell system and observing increased amyloid beta productions. Methods: We performed a PCR-based genetic analysis on APP, PSEN1 and PSEN2 in 100 Korean EOAD and 200 other dementia patients. PCR products were analyzed by Single-stranded conformation polymorphism (SSCP). Any alteration in the migration pattern in comparison to the normal control could suggest the presence and absence of mutation. For the confirmation of the mutation, samples were sequenced by traditional Sanger sequencing method. Pathogenic nature of the mutation was predicted by PolyPhen2 software for the comparison to the database, splice site prediction, and Raptor-X 3D modeling. Results: Several novel and known mutations in PSEN1 and PSEN2 were observed. In PSEN1 we found H163P (novel, published), T116I (novel in Asia), L226F (novel in Asia), L232P (novel) and G209A (novel). In PSEN2, V214L (novel, published) and R62C (known) were detected. Conclusions: In near future, we are planning to perform NGS studies to have better genetic profiling of Korean dementia patients.

CORRELATIONS BETWEEN VARIOUS MOCA COGNITIVE DOMAIN ASSESSMENTS AND REGIONAL BRAIN FDG-PET HYPOMETABOLISM

old. Three hundred fourteen (314) subjects have multiple MRIs, 52 have NP data , and 268 have genotype data at ADGC. After restricting to UDS visits within 180 days of a MRI (n1⁄41379), corresponding cognitive diagnoses consisted of 830 (60.2%) normal cognition, 308 (22.3%) mild cognitive impairment, and 241 (17.5%) dementia, among which 222 (92.1%) were primary probable or possible AD. Associated data from standardized assessments of behavioral and motor symptoms, functional activities, neurologic exam, and neuropsychological tests are also available. Conclusions: The NACC MRI Database is a large, freely available sample of MRIs that are linked to the rich, standardized UDS and NP data, as well as genotype data from ADGC.

WHITE MATTER ABNORMALITIES AND STRUCTURAL PARIETAL DISCONNECTIONS IN ALZHEIMER'S DISEASE

Lucas Porcello Schilling, Eduardo Rigon Zimmer, Antoine Leuzy, Andrea Lessa Benedet, Tharick Pascoal, Sara Mohades, Sulantha Mathotaarachch, Laksanun Cheewakriengkrai, Monica Shin, Maxime Parent, Min Su Kang, Sarinporn Manitsirikul, Daliah Farajat, Seqian Wang, Jessica Di Ciero, Thomas Beaudry, Simon Eskildsen, Jared Rowley, Felix Carbonell, Vladmir Fonov, Serge Gauthier, Pedro Rosa-Neto, McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; PUCRS, Porto Alegre, Quebec, Brazil; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; Aarhus University, Aarhus, Denmark. Canada; Biospective Inc., Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada. Contact e-mail: lucaspschilling@gmail.com

REGIONAL ASSOCIATION MAPS DESCRIBE DYNAMIC ARCHITECTURE OF AMYLOIDOSIS AND HYPOMETABOLISM IN ALZHEIMER'S DISEASE

IC-P-194 REGIONAL ASSOCIATION MAPS DESCRIBE DYNAMIC ARCHITECTURE OFAMYLOIDOSIS AND HYPOMETABOLISM IN ALZHEIMER’S DISEASE Sulantha Sanjeewa Mathotaarachchi, Sara Mohades, Eduardo Rigon Zimmer, Felix Carbonell, Thomas Beaudry, Maxime Parent, Andrea Lessa Benedet, Seqian Wang, Monica Shin, Vladimir S. Fonov, Laksanun Cheewakriengkrai, Antoine Leuzy, Lucas Porcello Schilling, Sarinporn Manitsirikul, Simon Eskildsen, Min Su Kang, Serge Gauthier, Pedro Rosa-Neto, McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Center-McGill Centre for Studies in Aging, Montreal, Quebec, Canada; McGill Center for Studies in Aging, Montreal, Quebec, Canada; Biospective Inc., Montreal, Quebec, Canada; McGill Centre for Studies in Aging, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill University, Porto Alegre, Brazil. Contact e-mail: sulantha.s@gmail.com

NEURODEGENERATION ASSOCIATED WITH LONGITUDINAL CHANGES OF AB1-42 AND FIBRILLARY AMYLOID

Background: Mutations in the Presenilin 1 (PSEN1) gene are associated with autosomal dominant early onset Alzheimer disease (EOAD). Posterior cerebral atrophy (PCA), a progressive neurodegenerative syndrome affecting visual processing accompanied by atrophy and hypometabolism in the parieto-occipital brain, has been associated with AD and certain PSEN1 gene mutations.Methods:Clinical, neuropsychological, and neuroimaging studies were performed. Postmortem neuropathologic studies of the brain were carried out. Histological methods included hematoxylinand eosin-Luxol fast blue and Thioflavin S. For immunohistochemistry, antibodies against b-amyloid, tau, and a-synuclein were used. DNA was extracted from brain or blood for gene sequencing. Results: At 47, the proband developed memory loss, unsteady gait, pyramidal signs, and visual disturbance (loss of depth perception, intermittent visual loss suggestive of a visual apraxia, eventual blindness.) MRI revealed greater atrophy in parietal than frontal lobes. DNA sequencing revealed an ATT to TTT nucleotide mutation, resulting in a phenylalanine for isoleucine substitution (I229F) in the PSEN1 gene. The proband’s daughters enrolled in the Dominantly Inherited Alzheimer Network. At 39, one daughter developed memory loss, unsteady gait, and visual disturbance. DNA sequencing confirmed a PSEN1 I229F mutation. Neuropsychological evaluation revealed inability to copy a simple geometric design, recall visual information, and a WAIS-R Block Design raw score of 0/51, indicating markedly impaired visuospatial abilities. Structural MRI revealed greater bilateral parieto-occipital lobe gray matter volume loss relative to frontal gray matter. FDG-PET confirmed notable hypometabolism in bilateral parietal lobes. PIB-PET showed high signal consistent with amyloid deposition throughout cortex, including parieto-occipital lobes. She died at 44. Histological and immunohistochemical studies confirmed AD in both brains. The proband’s brain showed severe cerebral atrophy of parieto-occipital lobes relative to the frontal and temporal lobes. The daughter’s brain showed disproportionate thinning of occipital cortex relative to other lobes and reduction of occipital white matter. In both brains, b-amyloid and tau burdens were severe in occipital cortex. The proband also had corticospinal tract degeneration. Conclusions: Prominent visual disturbances in EOADmay suggest the PCA syndrome. Our findings suggest that PCA may be associated with the PSEN1 I229F mutation. (Grants: P30AG35982, P30AG 010133, U19AG032438)

AMYLOIDOSIS CHANGES ASSOCIATIONS BETWEEN HIPPOCAMPUS VOLUME AND BRAIN METABOLIC DECLINES

BETWEEN HIPPOCAMPUS VOLUME AND BRAIN METABOLIC DECLINES Min Su Kang, Maxime Parent, Monica Shin, Eduardo Rigon Zimmer, Antonia Aliaga, Axel Mathieu, Sulantha Sanjeewa Mathotaarachchi, Sara Mohades, Sarinporn Manitsirikul, Jean-Paul Soucy, Serge Gauthier, Claudio Cuello, Pedro Rosa-Neto, McGill University, Verdun, Quebec, Canada; McGill University, Montreal, Quebec, Canada; McGill University, Montreal, Quebec, Canada; Douglas Hospital, Verdun, Quebec, Canada; 5 McGill Center-McGill Centre for Studies in Aging, Montreal, Quebec, Canada; 6 McGill Center for Studies in Aging, Montreal, Quebec, Canada; McGill University, Montreal, Quebec, Canada. Contact e-mail: peter.ms.kang@gmail.com