1. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    Acta Neuropathologica 131(6):935 (2016) PMID 27021906

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter,...
  2. "Missed" Mild Cognitive Impairment: High False-Negative Error Rate Based on Conventional Diagnostic Criteria.

    Journal of Alzheimer's Disease 52(2):685 (2016) PMID 27031477 PMCID PMC4879874

    Mild cognitive impairment (MCI) is typically diagnosed using subjective complaints, screening measures, clinical judgment, and a single memory score. Our prior work has shown that this method is highly susceptible to false-positive diagnostic errors. We examined whether the criteria also lead to...
  3. Cerebrospinal Fluid Particles in Alzheimer Disease and Parkinson Disease.

    Journal of Neuropathology & Experimental Neurology 74(7):672 (2015) PMID 26083568 PMCID PMC4471879

    Human cerebrospinal fluid (CSF) contains diverse lipid particles, including lipoproteins that are distinct from their plasma counterparts and contain apolipoprotein (apo) E isoforms, apoJ, and apoAI, and extracellular vesicles, which can be detected by annexin V binding. The aim of this study wa...
  4. Pulse pressure in relation to tau-mediated neurodegeneration, cerebral amyloidosis, and progression to dementia in very old adults.

    JAMA Neurology 72(5):546 (2015) PMID 25822631 PMCID PMC4428938

    Increased pulse pressure associated with age-related arterial stiffening increases risk for Alzheimer dementia but the mechanism responsible for this association remains unclear. To determine the relationship between pulse pressure and cerebral spinal fluid biomarker profiles of preclinical Alzh...
  5. Aggregate effects of vascular risk factors on cerebrovascular changes in autopsy-confirmed Alzheimer's disease.

    Alzheimer's & Dementia 11(4):394 (2015) PMID 25022538 PMCID PMC4287462

    We examined the relationships of antemortem vascular risk factors to postmortem cerebrovascular and Alzheimer's disease (AD) pathologies. Eighty-four AD patients underwent an assessment of vascular risk (blood pressure, cholesterol, smoking, cardiovascular disease, diabetes, atrial fibrillation,...
  6. Cerebrospinal fluid peptides as potential Parkinson disease biomarkers: a staged pipeline for discovery and validation.

    Molecular & Cellular Proteomics 14(3):544 (2015) PMID 25556233 PMCID PMC4349976

    Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throu...
  7. 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...
  8. Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans.

    Alzheimer's Research & Therapy 7(1):55 (2015) PMID 26244059 PMCID PMC4523931

    Ibuprofen is one of the nonsteroidal anti-inflammatory drugs that have been shown to selectively lower pathogenic amyloid beta-peptide (Aβ)42 without impairing overall γ-secretase activity in vitro. This γ-secretase modulator (GSM) activity has been hypothesized to contribute to the reduction in...
  9. Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer's Disease.

    Journal of Alzheimer's Disease 47(1):231 (2015) PMID 26402771 PMCID PMC4634634

    The NIA-AA criteria for "preclinical" Alzheimer's disease (AD) propose a staging method in which AD biomarkers follow an invariable temporal sequence in accordance with the amyloid cascade hypothesis. However, recent findings do not align with the proposed temporal sequence and "subtle cognitive...
  10. Increased CSF E-Selectin in Clinical Alzheimer's Disease without Altered CSF Aβ42 and Tau.

    Journal of Alzheimer's Disease 47(4):883 (2015) PMID 26401768

    Clinically diagnosed Alzheimer's disease (AD) is pathologically heterogeneous. In this multicenter cohort of 215 clinically diagnosed AD patients and 249 controls, E-selectin and vascular cell adhesion molecule 1 (VACM-1) were measured along with amyloid-β peptide 1-42 (Aβ42) and tau. We discove...
  11. 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...
  12. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease.

    Acta Neuropathologica 128(5):639 (2014) PMID 24997849 PMCID PMC4201967

    Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, ...
  13. Subjective cognitive complaints contribute to misdiagnosis of mild cognitive impairment.

    International Neuropsychological Society. Journal 20(8):836 (2014) PMID 25156329 PMCID PMC4172502

    Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer's Disease Neuroimaging Initiativ...
  14. Influence of lifestyle modifications on age-related free radical injury to brain.

    JAMA Neurology 71(9):1150 (2014) PMID 25048271 PMCID PMC4160350

    The Healthy Brain Initiative 2013-2018 seeks to optimize brain health as we age. Free radical injury is an important effector of molecular and cellular stress in the aging brain that derives from multiple sources. To identify potentially modifiable risk factors associated with increased markers ...
  15. Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.

    JAMA Neurology 71(6):742 (2014) PMID 24756381 PMCID PMC4051849

    Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascula...
  16. Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects.

    Neurobiology of Aging 35(2):357 (2014) PMID 24011543 PMCID PMC3859300

    Low cerebrospinal fluid (CSF) Aβ(42) levels correlate with increased brain Aβ deposition in Alzheimer's disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ(42) levels than non-carriers. The hypothesis of...
  17. Effect of TTP488 in patients with mild to moderate Alzheimer's disease.

    BMC Neurology 14:12 (2014) PMID 24423155 PMCID PMC4021072

    TTP488, an antagonist at the Receptor for Advanced Glycation End products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). A previous report describes decreased decline in ADAS-cog (delta = 3.1, p = 0.008 at 18 months, ANCOVA with multiple impu...
  18. Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults.

    Neurology 81(23):2024 (2013) PMID 24225352 PMCID PMC3854831

    The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including β-amyloid 1-42 (Aβ1-42) and phosphorylated tau (P-tau) protein, in cognitively normal older adults. One hundred seventy-seven cognitively normal, stroke-free older adu...
  19. Cerebrospinal fluid norepinephrine and cognition in subjects across the adult age span.

    Neurobiology of Aging 34(10):2287 (2013) PMID 23639207 PMCID PMC3706572

    Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships b...
  20. C9orf72 hexanucleotide repeat expansion and Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complex.

    JAMA Neurology 70(6):742 (2013) PMID 23588498 PMCID PMC3771869

    High-prevalence foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) exist in Japanese on the Kii Peninsula of Japan and in the Chamorros of Guam. Clinical and neuropathologic similarities suggest that the disease in these 2 populations may be related. Recent findi...