Clearing the amyloid in Alzheimer's: progress towards earlier diagnosis and effective treatments – an update for clinicians

References

• 1 Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimer Dementia 3(3), 186–191 (2007).
  MedlineGoogle Scholar
• 2 Whiley L, Sen A, Heaton J et al. Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. Neurobiol. Aging 35(2), 271–278 (2014).
  Medline CASGoogle Scholar
• 3 Drolle E, Hane F, Lee B, Leonenko Z. Atomic force microscopy to study molecular mechanisms of amyloid fibril formation and toxicity in Alzheimer's disease. Drug Metabol. Rev. 46(2), 207–223 (2014).
  Medline CASGoogle Scholar
• 4 Jarrett JT, Berger EP, Lansbury PT Jr. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32(18), 4693–4697 (1993).
  Medline CASGoogle Scholar
• 5 Dong S, Duan Y, Hu Y, Zhao Z. Advances in the pathogenesis of Alzheimer's disease: a re-evaluation of amyloid cascade hypothesis. Transl. Neurodegen. 1(1), 18 (2012).
  Medline CASGoogle Scholar
• 6 Bornebroek M, Haan J, Maat-Schieman ML, Van Duinen SG, Roos RA. Hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D): I – A review of clinical, radiologic and genetic aspects. Brain Pathol. 6(2), 111–114 (1996).
  Medline CASGoogle Scholar
• 7 Kumar-Singh S. Cerebral amyloid angiopathy: pathogenetic mechanisms and link to dense amyloid plaques. Genes Brain Behav. 7(Suppl. 1), 67–82 (2008).
  Medline CASGoogle Scholar
• 8 Weller RO, Massey A, Newman TA, Hutchings M, Kuo YM, Roher AE. Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Am. J. Pathol. 153(3), 725–733 (1998).
  Medline CASGoogle Scholar
• 9 Yamada M, Naiki H. Cerebral amyloid angiopathy. Prog. Mol. Biol. Translat. Sci. 107, 41–78 (2012).
  Medline CASGoogle Scholar
• 10 Ittner LM, Gotz J. Amyloid-beta and tau – a toxic pas de deux in Alzheimer's disease. Nat. Rev. Neurosci. 12(2), 65–72 (2011).
  Medline CASGoogle Scholar
• 11 Sorrentino G Bonavita V. Neurodegeneration and Alzheimer's disease: the lesson from tauopathies. Neurol. Sci. 28(2), 63–71 (2007).
  Medline CASGoogle Scholar
• 12 Stern Y. Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol 11(11), 1006–1012 (2012).
  MedlineGoogle Scholar
• 13 Wilson RS, Boyle PA, Yu L, Barnes LL, Schneider JA, Bennett DA. Life-span cognitive activity, neuropathologic burden, and cognitive aging. Neurology 81(4), 314–321 (2013).
  MedlineGoogle Scholar
• 14 Tanzi RE. A brief history of Alzheimer's disease gene discovery. J. Alzheimers Dis. 33(Suppl. 1), S5–S13 (2013).
  MedlineGoogle Scholar
• 15 Jonsson T, Atwal JK, Steinberg S et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488(7409), 96–99 (2012).
  Medline CASGoogle Scholar
• 16 Mawuenyega KG, Sigurdson W, Ovod V et al. Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 330(6012), 1774 (2010).
  Medline CASGoogle Scholar
• 17 Bates KA, Verdile G, Li QX et al. Clearance mechanisms of Alzheimer's amyloid-beta peptide: implications for therapeutic design and diagnostic tests. Mol. Psychiatry 14(5), 469–486 (2009).
  Medline CASGoogle Scholar
• 18 Miners JS, Barua N, Kehoe PG, Gill S, Love S. Abeta-degrading enzymes: potential for treatment of Alzheimer disease. J. Neuropathol. Exp. Neurol. 70(11), 944–959 (2011).
  Medline CASGoogle Scholar
• 19 Sharman MJ, Morici M, Hone E et al. APOE genotype results in differential effects on the peripheral clearance of amyloid-beta42 in APOE knock-in and knock-out mice. J. Alzheimers Dis. 21(2), 403–409 (2010).
  Medline CASGoogle Scholar
• 20 Morris JC, Roe CM, Xiong C et al. APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann. Neurol. 67(1), 122–131 (2010).
  Medline CASGoogle Scholar
• 21 Miners JS, Jones R, Love S. Differential changes in Abeta42 and Abeta40 with age. J. Alzheimers Dis. 40(3), 727–735 (2014).
  Medline CASGoogle Scholar
• 22 Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med. 14(2), 45–53 (2008).
  Medline CASGoogle Scholar
• 23 Aizenstein HJ, Nebes RD, Saxton JA et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch. Neurol. 65(11), 1509–1517 (2008).
  MedlineGoogle Scholar
• 24 Holtzman DM, Herz J, Bu G. Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harbor Persp. Med. 2(3), a006312 (2012).
  MedlineGoogle Scholar
• 25 Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol. Dis. Drug Target 8(1), 16–30 (2009).
  CASGoogle Scholar
• 26 Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol. 9(2), 106–118 (2013).
  Medline CASGoogle Scholar
• 27 Yang DS, Small DH, Seydel U et al. Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner. Neuroscience 90(4), 1217–1226 (1999).
  Medline CASGoogle Scholar
• 28 Tai LM, Mehra S, Shete V et al. Soluble apoE/Abeta complex: mechanism and therapeutic target for APOE4-induced AD risk. Mol. Neurodegen. 9, 2 (2014).
  MedlineGoogle Scholar
• 29 Luchsinger JA. Diabetes, related conditions, and dementia. J. Neurol. Sci. 299(1–2), 35–38 (2010).
  MedlineGoogle Scholar
• 30 Dash SK. Cognitive impairment and diabetes. Recent Patent Endocr. Metabol. Immune Drug Discov. 7(2), 155–165 (2013).
  Medline CASGoogle Scholar
• 31 De La Monte SM. Relationships Between Diabetes and Cognitive Impairment. Endocrinol. Metab. Clin. North Am. 43(1), 245–267 (2014).
  MedlineGoogle Scholar
• 32 Xu W, Qiu C, Gatz M, Pedersen NL, Johansson B, Fratiglioni L. Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study. Diabetes 58(1), 71–77 (2009).
  Medline CASGoogle Scholar
• 33 Strachan MW, Reynolds RM, Frier BM, Mitchell RJ, Price JF. The relationship between Type 2 diabetes and dementia. Br. Med. Bull. 88(1), 131–146 (2008).
  Medline CASGoogle Scholar
• 34 Zhao WQ, De Felice FG, Fernandez S et al. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J. 22(1), 246–260 (2008).
  Medline CASGoogle Scholar
• 35 Bomfim TR, Forny-Germano L, Sathler LB et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Abeta oligomers. J. Clin. Invest. 122(4), 1339–1353 (2012).
  Medline CASGoogle Scholar
• 36 Papadopoulos P, Rosa-Neto P, Rochford J, Hamel E. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-beta and cerebrovascular pathology. PLoS ONE 8(7), e68612 (2013).
  Medline CASGoogle Scholar
• 37 Freiherr J, Hallschmid M, Frey WH, 2nd et al. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs 27(7), 505–514 (2013).
  Medline CASGoogle Scholar
• 38 Brown BM, Peiffer JJ, Sohrabi HR et al. Intense physical activity is associated with cognitive performance in the elderly. Translat. Psychiatr. 2, e191 (2012).
  Medline CASGoogle Scholar
• 39 Lautenschlager NT, Cox KL, Flicker L et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA 300(9), 1027–1037 (2008).
  Medline CASGoogle Scholar
• 40 Hu N, Yu JT, Tan L, Wang YL, Sun L, Tan L. Nutrition and the risk of Alzheimer's disease. BioMed Res. Int. 524820 (2013).
  Google Scholar
• 41 Solfrizzi V, Panza F, Frisardi V et al. Diet and Alzheimer's disease risk factors or prevention: the current evidence. Expert Rev. Neurother. 11(5), 677–708 (2011).
  Medline CASGoogle Scholar
• 42 Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60(4), 652–656 (2003).
  Medline CASGoogle Scholar
• 43 Moreth J, Mavoungou C, Schindowski K. Is abeta a sufficient biomarker for monitoring anti-abeta clinical studies? A critical review. Front. Aging Neurosci. 5, 25 (2013).
  Medline CASGoogle Scholar
• 44 Henry MS, Passmore AP, Todd S, Mcguinness B, Craig D, Johnston JA. The development of effective biomarkers for Alzheimer's disease: a review. Int. J. Geriatr. Psychiatr. 28(4), 331–340 (2013).
  MedlineGoogle Scholar
• 45 Biagioni MC, Galvin JE. Using biomarkers to improve detection of Alzheimer's disease. Neurodegen. Dis. Manage. 1(2), 127–139 (2011).
  Google Scholar
• 46 Rosen C, Hansson O, Blennow K, Zetterberg H. Fluid biomarkers in Alzheimer's disease – current concepts. Mol. Neurodegen. 8, 20 (2013).
  MedlineGoogle Scholar
• 47 Andersson M, Zetterberg H, Minthon L, Blennow K, Londos E. The cognitive profile and CSF biomarkers in dementia with Lewy bodies and Parkinson's disease dementia. Int. J. Geriatr. Psychiatry 26(1), 100–105 (2011).
  Medline CASGoogle Scholar
• 48 Del Campo M, Mollenhauer B, Bertolotto A et al. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomarkers Med. 6(4), 419–430 (2012).
  CASGoogle Scholar
• 49 Parnetti L, Chiasserini D, Eusebi P et al. Performance of abeta1–40, abeta1–42, total tau, and phosphorylated tau as predictors of dementia in a cohort of patients with mild cognitive impairment. J. Alzheimers Dis. 29(1), 229–238 (2012).
  Medline CASGoogle Scholar
• 50 Lui JK, Laws SM, Li QX et al. Plasma amyloid-beta as a biomarker in Alzheimer's disease: the AIBL study of aging. J. Alzheimers Dis. 20(4), 1233–1242 (2010).
  Medline CASGoogle Scholar
• 51 Bateman RJ, Xiong C, Benzinger TL et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N. Engl. J. Med. 367(9), 795–804 (2012).
  Medline CASGoogle Scholar
• 52 Jack CR Jr, Knopman DS, Weigand SD et al. An operational approach to National Institute on Aging-Alzheimer's Association criteria for preclinical Alzheimer disease. Ann. Neurol. 71(6), 765–775 (2012).
  MedlineGoogle Scholar
• 53 Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron 80(6), 1347–1358 (2013).
  Medline CASGoogle Scholar
• 54 Shaffer JL, Petrella JR, Sheldon FC et al. Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers. Radiology 266(2), 583–591 (2013).
  MedlineGoogle Scholar
• 55 Ikonomovic MD, Klunk WE, Abrahamson EE et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 131(Pt 6), 1630–1645 (2008).
  MedlineGoogle Scholar
• 56 Mathis CA, Lopresti BJ, Klunk WE. Impact of amyloid imaging on drug development in Alzheimer's disease. Nuclear Med. Biol. 34(7), 809–822 (2007).
  Medline CASGoogle Scholar
• 57 Shin J, Lee SY, Kim SH, Kim YB, Cho SJ. Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer's disease. NeuroImage 43(2), 236–244 (2008).
  MedlineGoogle Scholar
• 58 Bacskai BJ, Frosch MP, Freeman SH et al. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch. Neurol. 64(3), 431–434 (2007).
  MedlineGoogle Scholar
• 59 Morris JC, Roe CM, Grant EA et al. Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Arch. Neurol. 66(12), 1469–1475 (2009).
  MedlineGoogle Scholar
• 60 Resnick SM, Sojkova J, Zhou Y et al. Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [¹¹C]PiB. Neurology 74(10), 807–815 (2010).
  Medline CASGoogle Scholar
• 61 Weigand SD, Vemuri P, Wiste HJ et al. Transforming cerebrospinal fluid Abeta42 measures into calculated Pittsburgh Compound B units of brain Abeta amyloid. Alzheimers Dement. 7(2), 133–141 (2011).
  Medline CASGoogle Scholar
• 62 Villemagne VL, Ataka S, Mizuno T et al. High striatal amyloid beta-peptide deposition across different autosomal Alzheimer disease mutation types. Arch. Neurol. 66(12), 1537–1544 (2009).
  MedlineGoogle Scholar
• 63 Raniga P, Bourgeat P, Fripp J et al. Automated (¹¹)C-PiB standardized uptake value ratio. Acad. Radiol. 15(11), 1376–1389 (2008).
  MedlineGoogle Scholar
• 64 Rowe CC, Ellis KA, Rimajova M et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol. Aging 31(8), 1275–1283 (2010).
  MedlineGoogle Scholar
• 65 Okello A, Koivunen J, Edison P et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an ¹¹C-PIB PET study. Neurology 73(10), 754–760 (2009).
  Medline CASGoogle Scholar
• 66 Bateman RJ, Xiong C, Benzinger TL et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N. Engl. J. Med. 367(9), 795–804 (2012).
  Medline CASGoogle Scholar
• 67 Rembach A, Watt AD, Wilson WJ et al. Plasma amyloid-beta levels are significantly associated with a transition toward Alzheimer's disease as measured by cognitive decline and change in neocortical amyloid burden. J. Alzheimers Dis. 40(1), 95–104 (2013).
  Google Scholar
• 68 Wang T, Xiao S, Liu Y et al. The efficacy of plasma biomarkers in early diagnosis of Alzheimer's disease. Int. J. Geriatr. Psychiatr. (2013).
  Google Scholar
• 69 Blennow K, De Meyer G, Hansson O et al. Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer's disease: a multicenter assessment. J. Nutr. Health Aging 13(3), 205–208 (2009).
  Medline CASGoogle Scholar
• 70 Ruiz A, Pesini P, Espinosa A et al. Blood amyloid beta levels in healthy, mild cognitive impairment and Alzheimer's disease individuals: replication of diastolic blood pressure correlations and analysis of critical covariates. PLoS ONE 8(11), e81334 (2013).
  MedlineGoogle Scholar
• 71 Fandrich M, Schmidt M, Grigorieff N. Recent progress in understanding Alzheimer's beta-amyloid structures. Trends Biochem. Sci. 36(6), 338–345 (2011).
  MedlineGoogle Scholar
• 72 Metti AL, Cauley JA. How predictive of dementia are peripheral inflammatory markers in the elderly? Neurodegener. Dis. Manag. 2(6), 609–622 (2012).
  Google Scholar
• 73 Arab L, Sadeghi R, Walker DG, Lue LF, Sabbagh MN. Consequences of aberrant insulin regulation in the brain: can treating diabetes be effective for Alzheimer's disease. Curr. Neuropharmacol. 9(4), 693–705 (2011).
  Medline CASGoogle Scholar
• 74 Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol. 6(3), 131–144 (2010).
  Medline CASGoogle Scholar
• 75 Pahnke J, Walker LC, Scheffler K, Krohn M. Alzheimer's disease and blood-brain barrier function – why have anti-beta-amyloid therapies failed to prevent dementia progression? Neurosci. Biobehav. Rev. 33(7), 1099–1108 (2009).
  Medline CASGoogle Scholar
• 76 Nygaard HB. Current and emerging therapies for Alzheimer's disease. Clin. Therapeut. 35(10), 1480–1489 (2013).
  Medline CASGoogle Scholar
• 77 Gotz J, Eckert A, Matamales M, Ittner LM, Liu X. Modes of Abeta toxicity in Alzheimer's disease. Cell. Mol. Life Sci. 68(20), 3359–3375 (2011).
  MedlineGoogle Scholar
• 78 Timmer NM, Kuiperij HB, De Waal RM, Verbeek MM. Do amyloid beta-associated factors co-deposit with Abeta in mouse models for Alzheimer's disease? J. Alzheimers Dis. 22(2), 345–355 (2010).
  Medline CASGoogle Scholar
• 79 Frost S, Kanagasingam Y, Sohrabi H et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer's disease. Translat. Psychiatr. 3, e233 (2013).
  Medline CASGoogle Scholar
• 80 Rowe C, Ellis K, Brown B et al. Cognition, hippocampal volume and fibrillar Aβ burden as predictors of cognitive decline: three-year follow-up results from AIBL. Alzheimer Dement. 8(4), P433 (2012).
  Google Scholar
• 81 Kim J, Onstead L, Randle S et al. Abeta40 inhibits amyloid deposition in vivo. J. Neurosci. 27(3), 627–633 (2007).
  Medline CASGoogle Scholar
• 82 Howlett DR. APP transgenic mice and their application to drug discovery. Histol. Histopathol. 26(12), 1611–1632 (2011).
  Medline CASGoogle Scholar
• 83 Pharmaceutical Research and Manufacturer's of America. Alzheimer's research: setbacks and stepping stones (2012).
  Google Scholar
• 84 ClinicalTrials.gov. US NIH. Studies found for Alzheimer's Organization. www.clinicaltrials.gov.
  Google Scholar
• 85 Imbimbo BP, Giardina GA. gamma-secretase inhibitors and modulators for the treatment of Alzheimer's disease: disappointments and hopes. Curr. Topics Med. Chem. 11(12), 1555–1570 (2011).
  Medline CASGoogle Scholar
• 86 Salloway S, Sperling R, Fox NC et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 370(4), 322–333 (2014).
  Medline CASGoogle Scholar
• 87 Aisen PS, Gauthier S, Ferris SH et al. Tramiprosate in mild-to-moderate Alzheimer's disease – a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase study). Arch. Med. Sci. 7(1), 102–111 (2011).
  Medline CASGoogle Scholar
• 88 Loeffler DA. Intravenous immunoglobulin and Alzheimer's disease: what now? J. Neuroinflam. 10(1), 70 (2013).
  Medline CASGoogle Scholar
• 89 Doody RS, Raman R, Farlow M et al. A Phase 3 trial of semagacestat for treatment of Alzheimer's disease. N. Engl. J. Med. 369(4), 341–350 (2013).
  Medline CASGoogle Scholar
• 90 Van Es JH, Van Gijn ME, Riccio O et al. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435(7044), 959–963 (2005).
  Medline CASGoogle Scholar
• 91 Wong GT, Manfra D, Poulet FM et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J. Biol. Chem. 279(13), 12876–12882 (2004).
  Medline CASGoogle Scholar
• 92 Gravitz L. Drugs: a tangled web of targets. Nature 475(7355), S9–11 (2011).
  Medline CASGoogle Scholar
• 93 Salloway S, Sperling R, Brashear HR. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. N. Engl. J. Med. 370(15), 1460 (2014).
  Medline CASGoogle Scholar
• 94 Prins ND, Scheltens P. Treating Alzheimer's disease with monoclonal antibodies: current status and outlook for the future. Alzheimers Res. Ther. 5(6), 56 (2013).
  MedlineGoogle Scholar
• 95 Panza F, Solfrizzi V, Imbimbo BP, Tortelli R, Santamato A, Logroscino G. Amyloid-based immunotherapy for Alzheimer's disease in the time of prevention trials: the way forward. Expert Rev. Clin. Immunol. 10(3), 405–419 (2014).
  Medline CASGoogle Scholar
• 96 Carrera I, Etcheverria I, Fernandez-Novoa L, Lombardi V, Cacabelos R, Vigo C. Vaccine development to treat Alzheimer's disease neuropathology in APP/PS1 transgenic mice. Int. J. Alzheimer's Dis. 2012, 376138 (2012).
  MedlineGoogle Scholar
• 97 Winblad B, Graf A, Riviere ME, Andreasen N, Ryan JM. Active immunotherapy options for Alzheimer's disease. Alzheimers Res. Ther. 6(1), 7 (2014).
  MedlineGoogle Scholar
• 98 Tan CC, Yu JT, Tan MS, Jiang T, Zhu XC, Tan L. Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy. Neurobiol. Aging 35(5), 941–957 (2014).
  MedlineGoogle Scholar
• 99 Wolfe DM, Lee JH, Kumar A, Lee S, Orenstein SJ, Nixon RA. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. Eur. J. Neurosci. 37(12), 1949–1961 (2013).
  MedlineGoogle Scholar
• 100 Pickford F, Masliah E, Britschgi M et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Investig. 118(6), 2190–2199 (2008).
  Medline CASGoogle Scholar
• 101 Bharadwaj PR, Verdile G, Barr RK et al. Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Abeta42 levels in yeast. J. Alzheimers Dis. 32(4), 949–967 (2012).
  Medline CASGoogle Scholar
• 102 Steele JW, Lachenmayer ML, Ju S et al. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model. Mol. Psychiatr. 18(8), 889–897 (2013).
  Medline CASGoogle Scholar
• 103 Bharadwaj PR, Bates KA, Porter T et al. Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer's and other neurodegenerative diseases. Translat. Psychiatr. 3, e332 (2013).
  Medline CASGoogle Scholar
• 104 Marchesi VT. Alzheimer's disease 2012: the great amyloid gamble. Am. J. Pathol. 180(5), 1762–1767 (2012).
  Medline CASGoogle Scholar
• 105 Kerbage C, Sadowsky CH, Jennings D, Cagle GD, Hartung PD. Alzheimer's disease diagnosis by detecting exogenous fluorescent signal of ligand bound to Beta amyloid in the lens of human eye: an exploratory study. Front. Neurol. 4, 62 (2013).
  MedlineGoogle Scholar
• 106 Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M. Retinal nerve fiber layer thickness in patients with Alzheimer disease. J. Neuroophthalmol. 33(1), 58–61 (2013).
  MedlineGoogle Scholar
• 107 Mandal PK, Joshi J, Saharan S. Visuospatial perception: an emerging biomarker for Alzheimer's disease. J. Alzheimers Dis. 31(Suppl. 3), S117–S135 (2012).
  MedlineGoogle Scholar