alzheimer disease


Summary: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)

Top Publications

  1. Dean D, Jerskey B, Chen K, Protas H, Thiyyagura P, Roontiva A, et al. Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA Neurol. 2014;71:11-22 pubmed publisher
    Converging evidence suggests brain structure alterations may precede overt cognitive impairment in Alzheimer disease by several decades...
  2. Cash D, Ridgway G, Liang Y, Ryan N, Kinnunen K, Yeatman T, et al. The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study. Neurology. 2013;81:1425-33 pubmed publisher
    To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers...
  3. Bonda D, Stone J, Torres S, Siedlak S, Perry G, Kryscio R, et al. Dysregulation of leptin signaling in Alzheimer disease: evidence for neuronal leptin resistance. J Neurochem. 2014;128:162-72 pubmed publisher
    Leptin signaling has received considerable attention in the Alzheimer disease (AD) field...
  4. Zotova E, Bharambe V, Cheaveau M, Morgan W, Holmes C, Harris S, et al. Inflammatory components in human Alzheimer's disease and after active amyloid-?42 immunization. Brain. 2013;136:2677-96 pubmed publisher
    ..The results suggest that, in the long term, amyloid-? immunotherapy results in downregulation of microglial activation and potentially reduces the inflammation-mediated component of the neurodegeneration of Alzheimer's disease. ..
  5. Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844-66 pubmed publisher
    ..Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. ..
  6. Bloom G. Amyloid-? and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014;71:505-8 pubmed publisher
    The defining features of Alzheimer disease (AD) include conspicuous changes in both brain histology and behavior...
  7. Galasko D, BELL J, Mancuso J, Kupiec J, Sabbagh M, van Dyck C, et al. Clinical trial of an inhibitor of RAGE-A? interactions in Alzheimer disease. Neurology. 2014;82:1536-42 pubmed publisher
    ..of PF-04494700, an inhibitor of the receptor for advanced glycation end products (RAGE), in mild to moderate Alzheimer disease (AD). Double-blind, placebo-controlled trial at 40 academic centers (United States)...
  8. Reinhardt S, Schuck F, Grösgen S, Riemenschneider M, Hartmann T, Postina R, et al. Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer's disease. FASEB J. 2014;28:978-97 pubmed publisher
    ..Our results demonstrate that XBP-1 is a driver of ADAM10 gene expression and that disturbance of this pathway might contribute to development or progression of AD. ..
  9. Mills S, Mallmann J, Santacruz A, Fuqua A, Carril M, Aisen P, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013;169:737-43 pubmed publisher

More Information


  1. Kanekiyo T, Xu H, Bu G. ApoE and A? in Alzheimer's disease: accidental encounters or partners?. Neuron. 2014;81:740-54 pubmed publisher
  2. Schedin Weiss S, Winblad B, Tjernberg L. The role of protein glycosylation in Alzheimer disease. FEBS J. 2014;281:46-62 pubmed publisher
    ..This review serves to highlight the role of protein glycosylation in Alzheimer disease (AD), a topic that has not been thoroughly investigated, although glycosylation defects have been observed ..
  3. Pooler A, Noble W, Hanger D. A role for tau at the synapse in Alzheimer's disease pathogenesis. Neuropharmacology. 2014;76 Pt A:1-8 pubmed publisher
    ..This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. ..
  4. Vos S, Xiong C, Visser P, Jasielec M, Hassenstab J, Grant E, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013;12:957-65 pubmed publisher
  5. Mondragón Rodríguez S, Perry G, Zhu X, Moreira P, Acevedo Aquino M, Williams S. Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer's disease. Oxid Med Cell Longev. 2013;2013:940603 pubmed publisher
  6. Lim A, Yu L, Kowgier M, Schneider J, Buchman A, Bennett D. Modification of the relationship of the apolipoprotein E ?4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurol. 2013;70:1544-51 pubmed publisher
    ..E (APOE [GenBank, 348; OMIM, 107741]) ?4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD)...
  7. Musicco M, Adorni F, Di Santo S, Prinelli F, Pettenati C, Caltagirone C, et al. Inverse occurrence of cancer and Alzheimer disease: a population-based incidence study. Neurology. 2013;81:322-8 pubmed publisher
    To evaluate the incidence of cancer in persons with Alzheimer disease (AD) and the incidence of AD dementia in persons with cancer. This was a cohort study in Northern Italy on more than 1 million residents...
  8. Lau P, Bossers K, Janky R, Salta E, Frigerio C, Barbash S, et al. Alteration of the microRNA network during the progression of Alzheimer's disease. EMBO Mol Med. 2013;5:1613-34 pubmed publisher
    ..We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway. ..
  9. Dubois B, Epelbaum S, Santos A, Di Stefano F, Julian A, Michon A, et al. Alzheimer disease: from biomarkers to diagnosis. Rev Neurol (Paris). 2013;169:744-51 pubmed publisher
  10. van Harten A, Smits L, Teunissen C, Visser P, Koene T, Blankenstein M, et al. Preclinical AD predicts decline in memory and executive functions in subjective complaints. Neurology. 2013;81:1409-16 pubmed publisher
    We assessed whether preclinical Alzheimer disease (AD) based on CSF biomarkers at baseline predicts decline in cognitive functioning as measured by repeated neuropsychological tests for 4 cognitive domains in patients with subjective ..
  11. Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, et al. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates A?42-induced Alzheimer's disease-like symptoms. Neurobiol Aging. 2013;34:2604-12 pubmed publisher
    ..Early manipulation of brain copper uptake can have a great effect on A? pathology. ..
  12. Benzinger T, Blazey T, Jack C, Koeppe R, Su Y, Xiong C, et al. Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease. Proc Natl Acad Sci U S A. 2013;110:E4502-9 pubmed publisher
    ..Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease. ..
  13. Westwood A, Beiser A, DeCarli C, Harris T, Chen T, He X, et al. Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy. Neurology. 2014;82:1613-9 pubmed publisher
    To relate serum insulin-like growth factor-1 (IGF-1) to risk of Alzheimer disease (AD) dementia and to brain volumes in a dementia-free community sample spanning middle and older ages.
  14. Vardarajan B, Faber K, Bird T, Bennett D, Rosenberg R, Boeve B, et al. Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD/NCRAD and EFIGA families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and. JAMA Neurol. 2014;71:315-23 pubmed publisher
    Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia...
  15. Kim S, Swaminathan S, Inlow M, Risacher S, Nho K, Shen L, et al. Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel. PLoS ONE. 2013;8:e70269 pubmed publisher
    ..With intensive searches taking place for proteomic biomarkers for many diseases, the role of genetic variation takes on new importance and should be considered in interpretation of proteomic results. ..
  16. Sala Frigerio C, Lau P, Salta E, Tournoy J, Bossers K, Vandenberghe R, et al. Reduced expression of hsa-miR-27a-3p in CSF of patients with Alzheimer disease. Neurology. 2013;81:2103-6 pubmed publisher
    We evaluated microRNAs (miRNAs) as potential biomarkers for Alzheimer disease (AD) by analyzing the expression level of miRNAs in CSF of patients with AD dementia and nonaffected control subjects...
  17. Machulda M, Pankratz V, Christianson T, Ivnik R, Mielke M, Roberts R, et al. Practice effects and longitudinal cognitive change in normal aging vs. incident mild cognitive impairment and dementia in the Mayo Clinic Study of Aging. Clin Neuropsychol. 2013;27:1247-64 pubmed publisher
    ..Modeling cognitive change in an epidemiologic sample may serve as a useful benchmark for evaluating cognitive change in future intervention studies. ..
  18. Morozova O, March Z, Robinson A, Colby D. Conformational features of tau fibrils from Alzheimer's disease brain are faithfully propagated by unmodified recombinant protein. Biochemistry. 2013;52:6960-7 pubmed publisher
    ..These results also demonstrate that post-translational modifications such as phosphorylation are not a prerequisite for the propagation of the tau fibril conformation found in AD. ..
  19. Doody R, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013;369:341-50 pubmed publisher
    ..Semagacestat was associated with more adverse events, including skin cancers and infections. (Funded by Eli Lilly; number, NCT00594568.) ..
  20. Koleske A. Molecular mechanisms of dendrite stability. Nat Rev Neurosci. 2013;14:536-50 pubmed publisher
    ..Recent findings have provided insights into the molecular mechanisms that underlie long-term dendrite stabilization, how these mechanisms differ from those used to mediate structural plasticity and how they are disrupted in disease. ..
  21. Doody R, Thomas R, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:311-21 pubmed publisher
    ..49). Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. (Funded by Eli Lilly; EXPEDITION 1 and 2 numbers, NCT00905372 and NCT00904683.). ..
  22. Monson N, Ireland S, Ligocki A, Chen D, Rounds W, Li M, et al. Elevated CNS inflammation in patients with preclinical Alzheimer's disease. J Cereb Blood Flow Metab. 2014;34:30-3 pubmed publisher
    ..Thus, brain inflammation occurs early at the preclinical stage of AD and may have an important role in pathology. ..
  23. Wischik C, Harrington C, Storey J. Tau-aggregation inhibitor therapy for Alzheimer's disease. Biochem Pharmacol. 2014;88:529-39 pubmed publisher
    ..Phase 3 trials are underway with a novel stabilized reduced form of methylthioninium (LMTX) that has improved tolerability and absorption. ..
  24. Harper L, Barkhof F, Scheltens P, Schott J, Fox N. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry. 2014;85:692-8 pubmed publisher
    ..In this article we describe the characteristic MRI findings of the various dementias and provide a structured algorithm with the aim of providing clinicians with a practical guide to assessing scans. ..
  25. Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79:1094-108 pubmed publisher
    ..11)C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [(11)C]PBB3 signals were found in a corticobasal syndrome patient negative for [(11)C]PIB-PET. ..
  26. Reitz C, Mayeux R. Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochem Pharmacol. 2014;88:640-51 pubmed publisher
    ..In the US alone, Alzheimer disease (AD) - the most frequent cause of dementia characterized by a progressive decline in cognitive function in ..
  27. Dysken M, Sano M, Asthana S, Vertrees J, Pallaki M, Llorente M, et al. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311:33-44 pubmed publisher
    Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD...
  28. Shulman J, Chen K, Keenan B, Chibnik L, Fleisher A, Thiyyagura P, et al. Genetic susceptibility for Alzheimer disease neuritic plaque pathology. JAMA Neurol. 2013;70:1150-7 pubmed publisher
    While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques...
  29. Yang Y, Cudaback E, Jorstad N, Hemingway J, Hagan C, Melief E, et al. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease. Am J Pathol. 2013;183:905-17 pubmed publisher
    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia...
  30. Zhang D, Pekkanen Mattila M, Shahsavani M, Falk A, Teixeira A, Herland A. A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons. Biomaterials. 2014;35:1420-8 pubmed publisher
    ..We propose that the 3D in vitro model has higher resemblance to the AD pathology than conventional 2D cultures and could be used in further studies of the disease. ..
  31. Amieva H, Mokri H, Le Goff M, Meillon C, Jacqmin Gadda H, Foubert Samier A, et al. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline. Brain. 2014;137:1167-75 pubmed publisher
    ..In contrast, higher education protects against further cognitive decline for ?7 years until pathology becomes more severe. ..
  32. Ma Q, Zuo X, Yang F, Ubeda O, Gant D, Alaverdyan M, et al. Loss of MAP function leads to hippocampal synapse loss and deficits in the Morris Water Maze with aging. J Neurosci. 2014;34:7124-36 pubmed publisher
    ..Therefore, in addition to microtubule-stabilizing therapeutic drugs, preserving or restoring compensatory MAP function may be a useful new prevention strategy. ..
  33. Rockenstein E, Nuber S, Overk C, Ubhi K, Mante M, Patrick C, et al. Accumulation of oligomer-prone ?-synuclein exacerbates synaptic and neuronal degeneration in vivo. Brain. 2014;137:1496-513 pubmed publisher
    ..This oligomer-prone model might be useful for evaluating therapies directed at oligomer reduction. ..
  34. Cheng S, Cao D, Hottman D, Yuan L, Bergo M, Li L. Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer disease. J Biol Chem. 2013;288:35952-60 pubmed publisher
    Isoprenoids and prenylated proteins have been implicated in the pathophysiology of Alzheimer disease (AD), including amyloid-? precursor protein metabolism, Tau phosphorylation, synaptic plasticity, and neuroinflammation...
  35. Do Carmo S, Cuello A. Modeling Alzheimer's disease in transgenic rats. Mol Neurodegener. 2013;8:37 pubmed publisher
    ..Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. ..
  36. Erten Lyons D, Woltjer R, Kaye J, Mattek N, Dodge H, Green S, et al. Neuropathologic basis of white matter hyperintensity accumulation with advanced age. Neurology. 2013;81:977-83 pubmed publisher
    ..measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation...
  37. Forabosco P, Ramasamy A, Trabzuni D, Walker R, Smith C, Bras J, et al. Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol Aging. 2013;34:2699-714 pubmed publisher
  38. Imtiaz B, Tolppanen A, Kivipelto M, Soininen H. Future directions in Alzheimer's disease from risk factors to prevention. Biochem Pharmacol. 2014;88:661-70 pubmed publisher
  39. Wilcock D, Griffin W. Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis. J Neuroinflammation. 2013;10:84 pubmed publisher
  40. Kovacs G, Milenkovic I, Wöhrer A, Hoftberger R, Gelpi E, Haberler C, et al. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013;126:365-84 pubmed publisher
    ..This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients. ..
  41. Erickson M, Banks W. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease. J Cereb Blood Flow Metab. 2013;33:1500-13 pubmed publisher
    ..From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of A? pathology. ..
  42. Zhu Z, Yan J, Jiang W, Yao X, Chen J, Chen L, et al. Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both ?-amyloid production and clearance. J Neurosci. 2013;33:13138-49 pubmed publisher
  43. Muller M, Kuiperij H, Claassen J, Kusters B, Verbeek M. MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid. Neurobiol Aging. 2014;35:152-8 pubmed publisher
    ..In conclusion, the abnormal expression of several miRNAs in hippocampus of intermediate- and late-stage AD patients suggests their involvement in AD pathogenesis, and low levels of miR-146a in CSF were associated with AD. ..
  44. Matsumoto Y, Niimi N, Kohyama K. Development of a new DNA vaccine for Alzheimer disease targeting a wide range of a? species and amyloidogenic peptides. PLoS ONE. 2013;8:e75203 pubmed publisher
    ..that not only A? oligomers, but also other A? species and amyloidogenic peptides are neurotoxic in Alzheimer disease (AD) and play a pivotal role in AD pathogenesis...
  45. Siman R, Lin Y, Malthankar Phatak G, Dong Y. A rapid gene delivery-based mouse model for early-stage Alzheimer disease-type tauopathy. J Neuropathol Exp Neurol. 2013;72:1062-71 pubmed publisher
    ..memory and develops tau and amyloid pathologies and progressive degeneration starting in the early stages of Alzheimer disease (AD)...
  46. Parra Damas A, Valero J, Chen M, España J, Martín E, Ferrer I, et al. Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages. J Neurosci. 2014;34:5776-87 pubmed publisher
    ..Our results reveal a critical role of Crtc1-dependent transcription on spatial memory formation and provide the first evidence that targeting brain transcriptome reverses memory loss in AD. ..
  47. Vandal M, Alata W, Tremblay C, Rioux Perreault C, Salem N, Calon F, et al. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2. J Neurochem. 2014;129:516-26 pubmed publisher
    ..These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD). ..
  48. Solomon A, Mangialasche F, Richard E, Andrieu S, Bennett D, Breteler M, et al. Advances in the prevention of Alzheimer's disease and dementia. J Intern Med. 2014;275:229-50 pubmed publisher
  49. Hostage C, Choudhury K, Murali Doraiswamy P, Petrella J. Mapping the effect of the apolipoprotein E genotype on 4-year atrophy rates in an Alzheimer disease-related brain network. Radiology. 2014;271:211-9 pubmed publisher
    To determine the effect of the apolipoprotein E (APOE) genotype on atrophy rates of specific brain gray matter regions hypothesized to be key components of cognitive networks disrupted in Alzheimer disease.
  50. Mapstone M, Cheema A, Fiandaca M, Zhong X, Mhyre T, MacArthur L, et al. Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med. 2014;20:415-8 pubmed publisher
    ..This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease. ..
  51. Marques F, Sousa J, Sousa N, Palha J. Blood-brain-barriers in aging and in Alzheimer's disease. Mol Neurodegener. 2013;8:38 pubmed publisher
    ..Herein, we provide a review on how the brain barriers change during aging and in AD and how these processes impact on brain function. ..
  52. Dubois B, Feldman H, Jacova C, Hampel H, Molinuevo J, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614-29 pubmed publisher
    ..This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD. ..