1. Distinct Lysosomal Network Protein Profiles in Parkinsonian Syndrome Cerebrospinal Fluid.

    Journal of Parkinson's Disease 6(2):307 (2016) PMID 27061067 PMCID PMC4927933

    Clinical diagnosis of parkinsonian syndromes like Parkinson's disease (PD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is hampered by overlapping symptomatology and lack of diagnostic biomarkers, and definitive diagnosis is only possible post-mortem. Since impaired ...
  2. Progranulin as a candidate biomarker for therapeutic trial in patients with ALS and FTLD.

    Journal of Neural Transmission 123(3):289 (2016) PMID 26659729

    The loss-of-function mechanism in progranulin (PGRN) mutation carriers makes PGRN an interesting target for upregulation as a therapeutic approach in neurodegenerative diseases like frontotemporal lobar degeneration. This gives rise to several questions: (1) how stable are PGRN levels in blood a...
  3. Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage.

    Neurology 86(7):600 (2016) PMID 26802093 PMCID PMC4762418

    To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease. We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of pa...
  4. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease.

    Neurology 85(1):40 (2015) PMID 26062630 PMCID PMC4501943

    Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients w...
  5. Low neural exosomal levels of cellular survival factors in Alzheimer's disease.

    Annals of clinical and translational neurology 2(7):769 (2015) PMID 26273689 PMCID PMC4531059

    Transcription factors that mediate neuronal defenses against diverse stresses were quantified in plasma neural-derived exosomes of Alzheimer's disease or frontotemporal dementia patients and matched controls. Exosomal levels of low-density lipoprotein receptor-related protein 6, heat-shock facto...
  6. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.

    Alzheimer's & Dementia 11(6):600 (2015) PMID 25130657 PMCID PMC4329112

    Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two ...
  7. Bayesian segmentation of brainstem structures in MRI.

    NeuroImage 113:184 (2015) PMID 25776214 PMCID PMC4434226

    In this paper we present a method to segment four brainstem structures (midbrain, pons, medulla oblongata and superior cerebellar peduncle) from 3D brain MRI scans. The segmentation method relies on a probabilistic atlas of the brainstem and its neighboring brain structures. To build the atlas, ...
  8. A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy.

    JAMA Neurology 72(4):414 (2015) PMID 25706306 PMCID PMC4397175

    Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wi...
  9. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer's disease.

    FASEB Journal 29(2):589 (2015) PMID 25342129 PMCID PMC4314222

    Insulin resistance causes diminished glucose uptake in similar regions of the brain in Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2). Brain tissue studies suggested that insulin resistance is caused by low insulin receptor signaling attributable to its abnormal association with mor...
  10. Rarity of the Alzheimer disease-protective APP A673T variant in the United States.
    Li-San Wang, Adam C Naj, Robert Graham, Paul K Crane, Brian W Kunkle, Carlos Cruchaga, Josue D Gonzalez Murcia, Lisa Cannon-Albright, Clinton T Baldwin, Henrik Zetterberg, Kaj Blennow, Walter A Kukull, Kelley M Faber, Nicole Schupf, Maria C Norton, JoAnn Tschanz, Ronald G Munger, Christopher D Corcoran, Ekaterina Rogaeva, Chiao-Feng Lin, Beth A Dombroski, Laura B Cantwell, Amanda Partch, Otto Valladares, Hakon Hakonarson, Peter St George-Hyslop, Robert C Green, Alison M Goate, Tatiana M Foroud, Regina M Carney, Eric B Larson, Timothy W Behrens, John S Kauwe, Jonathan L Haines, Lindsay A Farrer, Margaret A Pericak-Vance, Richard Mayeux, Gerard D Schellenberg, Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Michael Barmada, Lisa Barnes, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, David A Bennett, Eileen H Bigio, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Steven L Carroll, Helena Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, F Yesim Demirci, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Nilufer Ertekin-Taner, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, Neill R Graff-Radford, John H Growdon, Ronald L Hamilton, Kara L Hamilton-Nelson, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Gregory A Jicha, Lee-Way Jin, Gyungah Jun, Gyungah Jun, M Ilyas Kamboh, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James Lah, James B Leverenz, Allan I Levey, Gei Li, Andrew P Lieberman, Oscar Lopez, Kathryn Lunetta, Constantine G Lyketsos, Wendy J Mack, Daniel C Marson, Eden R Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan McCurry, Andrew N McDavid, Ann C McKee, W Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, John C Morris, Jill R Murrell, John M Olichney, Joseph E Parisi, William Perry, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon Schneider, William Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Debby W Tsuang, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, and Lei Yu

    JAMA Neurology 72(2):209 (2015) PMID 25531812 PMCID PMC4324097

    Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this varia...
  11. An algorithm for optimal fusion of atlases with different labeling protocols.

    NeuroImage 106:451 (2015) PMID 25463466 PMCID PMC4286284

    In this paper we present a novel label fusion algorithm suited for scenarios in which different manual delineation protocols with potentially disparate structures have been used to annotate the training scans (hereafter referred to as "atlases"). Such scenarios arise when atlases have missing st...
  12. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability.

    Neurology 84(2):174 (2015) PMID 25503617 PMCID PMC4336088

    To determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD). We conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to te...
  13. Temporal Structure of Human Gaze Dynamics Is Invariant During Free Viewing.

    PLoS ONE 10(9):e0139379 (2015) PMID 26421613 PMCID PMC4589360

    We investigate the dynamic structure of human gaze and present an experimental study of the frequency components of the change in gaze position over time during free viewing of computer-generated fractal images. We show that changes in gaze position are scale-invariant in time with statistical p...
  14. Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.
    Adam C Naj, Gyungah Jun, Christiane Reitz, Brian W Kunkle, William Perry, Yo Son Park, Gary W Beecham, Ruchita A Rajbhandary, Kara L Hamilton-Nelson, Li-San Wang, John S Kauwe, Matthew J Huentelman, Amanda J Myers, Thomas D Bird, Bradley F Boeve, Clinton T Baldwin, Gail P Jarvik, Paul K Crane, Ekaterina Rogaeva, Michael Barmada, F Yesim Demirci, Carlos Cruchaga, Patricia L Kramer, Nilufer Ertekin-Taner, John Hardy, Neill R Graff-Radford, Robert C Green, Eric B Larson, Peter H St George-Hyslop, Joseph D Buxbaum, Denis A Evans, Julie A Schneider, Kathryn Lunetta, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, Philip L De Jager, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Eden R Martin, Jonathan L Haines, Richard P Mayeux, Lindsay A Farrer, Gerard D Schellenberg, Margaret A Pericak-Vance, Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Lisa Barnes, Thomas G Beach, James T Becker, Duane Beekly, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Chris S Carlson, Regina M Carney, Minerva Carrasquillo, Steven L Carroll, Helena Chui, David G Clark, Jason Corneveaux, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Chiao-Feng Lin, Oscar Lopez, Constantine G Lyketsos, Wendy J Mack, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Jill R Murrell, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Lon Schneider, William Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Otto Valladares, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, and Lei Yu

    JAMA Neurology 71(11):1394 (2014) PMID 25199842 PMCID PMC4314944

    Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants. To investigate the effects of known Alzheimer disease risk lo...
  15. LONGITUDINAL WHITE MATTER MICROSTRUCTURAL CHANGES IN FRONTOTEMPORAL LOBAR DEGENERATION SUBTYPES

    Alzheimer's & Dementia 10(4):P407 (2014)

  16. LONGITUDINAL WHITE MATTER MICROSTRUCTURAL CHANGES IN FRONTOTEMPORAL LOBAR DEGENERATION SUBTYPES

    Alzheimer's & Dementia 10(4):P44 (2014)

  17. PATHOGENIC PROTEINS IN NEURALLY-DERIVED BLOOD EXOSOMES AS NEAR-PERFECT DIAGNOSTIC AND PROGNOSTIC BIOMARKERS FOR ALZHEIMER'S DISEASE

    Alzheimer's & Dementia 10(4):P281 (2014)

  18. Demographic and neuropsychiatric factors associated with off-label medication use in frontotemporal dementia and Alzheimer's disease.

    Alzheimer Disease and Associated Disorders 28(2):182 (2014) PMID 23995817 PMCID PMC3938980

    Off-label medication use for treating cognitive impairments and neuropsychiatric symptoms occurs in frontotemporal dementia (FTD) and Alzheimer disease (AD). We compared the use of cognitive and psychiatric medications in FTD and AD and evaluated the relationship between neuropsychiatric symptom...
  19. PET imaging of neuropathology in tauopathies: progressive supranuclear palsy.

    Journal of Alzheimer's Disease 36(1):145 (2013) PMID 23579330 PMCID PMC3674205

    Currently [18F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [18F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supran...
  20. Novel late-onset Alzheimer disease loci variants associate with brain gene expression.
    Mariet Allen, Fanggeng Zou, High Seng Chai, Curtis S Younkin, Julia Crook, V Shane Pankratz, Minerva Carrasquillo, Christopher N Rowley, Asha Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly G Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Debra Schultz, Fariborz Rakhshan, Christopher P Kolbert, Jin Jen, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Gerard D Schellenberg, Ronald C Petersen, Neill R Graff-Radford, Dennis W Dickson, Steven G Younkin, Nilüfer Ertekin-Taner, Liana G Apostolova, Steven E Arnold, Clinton T Baldwin, Robert Barber, Michael Barmada, Thomas Beach, Gary W Beecham, Duane Beekly, David A Bennett, Eileen H Bigio, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Jacqueline Buros, Joseph D Buxbaum, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Chris S Carlson, Regina M Carney, Steven L Carroll, Helena Chui, David G Clark, Jason Corneveaux, Carl W Cotman, Paul K Crane, Carlos Cruchaga, Jeffrey L Cummings, Philip L De Jager, Charles DeCarli, Steven T DeKosky, F Yesim Demirci, Ramon Diaz-Arrastia, Malcolm Dick, Beth A Dombroski, Ranjan Duara, William D Ellis, Denis Evans, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Tatiana M Foroud, Matthew Frosch, Douglas R Galasko, Paul J Gallins, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Sid Gilman, Bruno Giordani, Jonathan D Glass, Alison M Goate, Robert C Green, John H Growdon, Hakon Hakonarson, Ronald L Hamilton, John Hardy, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Gregory A Jicha, Lee-Way Jin, Gyungah Jun, M Ilyas Kamboh, Jason Karlawish, Anna Karydas, John S Kauwe, Jeffrey A Kaye, Nancy Kennedy, Ronald Kim, Edward H Koo, Neil W Kowall, Patricia Kramer, Walter A Kukull, James Lah, Eric B Larson, Allan I Levey, Andrew P Lieberman, Oscar Lopez, Kathryn Lunetta, Wendy J Mack, Daniel C Marson, Eden R Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, John C Morris, Amanda J Myers, Adam C Naj, Petra Nowotny, Joseph E Parisi, Daniel Perl, Elaine Peskind, Wayne Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Ruchita A Rajbhandary, Murray Raskind, Eric M Reiman, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Ekaterina Rogaeva, Roger N Rosenberg, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon Schneider, William Seeley, Michael L Shelanski, Michael A Slifer, Charles D Smith, Joshua A Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert A Stern, Rudolph E Tanzi, John Q Trojanowski, Juan C Troncoso, Debby W Tsuang, Vivianna M Van Deerlin, Badri Narayan Vardarajan, Harry Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, and Randall L Woltjer

    Neurology 79(3):221 (2012) PMID 22722634 PMCID PMC3398432

    Recent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expressi...