Cerebrospinal fluid biomarkers of Alzheimer’s disease

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

• 1  Mirra S, Heyman A, McKeel D et al.: The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology41,479–486 (1991).
  Medline CASGoogle Scholar
• 2  Khachaturian Z: Diagnosis of Alzheimer’s disease. Arch. Neurol.42,1097–1105 (1985).
  Medline CASGoogle Scholar
• 3  Hyman B, Trojanowski J: Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer disease. J. Neuropathol. Exp. Neurol.56,1095–1097 (1997).
  Medline CASGoogle Scholar
• 4  Morris J: The clinical dementia rating (CDR). Current version and scoring rules. Neurology43,2412–2414 (1993).
  Medline CASGoogle Scholar
• 5  Petersen R, Smith G, Waring S, Ivnik R, Tabgalos E, Kokmen E: Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol.56,303–308 (1999).
  Medline CASGoogle Scholar
• 6  Storandt M, Grant E, Miller J, Morris J: Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI. Neurology67,467–473 (2006).
  MedlineGoogle Scholar
• 7  Price J, Ko A, Wade M, Tsou S, McKeel D, Morris J: Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer’s disease. Arch. Neurol.58,1395–1402 (2001).
  Medline CASGoogle Scholar
• 8  Morris J, Storandt M, Miller J et al.: Mild cognitive impairment represents early-stage Alzheimer’s disease. Arch. Neurol.58,397–405 (2001).
  Medline CASGoogle Scholar
• 9  Cummings J, Jeste D: Alzheimer’s disease and its management in the year 2010. Psychiatr. Serv.50,1173–1177 (1999).
  Medline CASGoogle Scholar
• 10  Teel C: Rural practitioners’ experiences in dementia diagnosis and treatment. Aging Ment. Health8,422–429 (2004).
  Medline CASGoogle Scholar
• 11  Braak H, Braak E: Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol. Aging18,351–357 (1997).▪ A classic neuropathological study that defines the neuroanatomical development of Alzheimer’s disease (AD) neuropathological lesions with aging.
  Medline CASGoogle Scholar
• 12  Price J, Mckeel D, Buckles V et al.: Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease. Neurobiol. Aging30,1026–1036 (2009).
  MedlineGoogle Scholar
• 13  Evans D, Funkenstein H, Albert M et al.: Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA262,2551–2556 (1989).
  Medline CASGoogle Scholar
• 14  Morris J, Price J: Pathologic correlates of nondemented aging, mild cognitive impairment, and early stage Alzheimer’s disease. J. Mol. Neurosci.17,101–118 (2001).▪ Clinicopathological study correlating AD lesions with different stages of aging and development of AD dementia.
  Medline CASGoogle Scholar
• 15  Gomez-Isla T, Price J, McKeel D, Morris J, Growdon J, Hyman B: Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J. Neurosci.16,4491–4500 (1996).
  Medline CASGoogle Scholar
• 16  Markesbery W, Schmitt F, Kryscio R, Davis D, Smith C, Wekstein D: Neuropathologic substrate of mild cognitive impairment. Arch. Neurol.63,38–46 (2006).
  MedlineGoogle Scholar
• 17  Brody D, Magnoni S, Schwetye K et al.: Amyloid-β dynamics correlate with neurological status in the injured human brain. Science321,1221–1224 (2008).▪ Elegant study using intracerebral microdialysis in living patients suffering from acute brain injury to measure analytes in serial samples of brain interstitial fluid and demonstrates a correlation between changes in amyloid-β (Aβ) concentration and neurological status.
  Medline CASGoogle Scholar
• 18  Hardy J, Selkoe D: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science297,353–356 (2002).
  Medline CASGoogle Scholar
• 19  Wiltfang J, Esselmann H, Bibl M et al.: Amyloid β peptide ratio 42/40 but not Aβ 42 correlates with phospho-tau in patients with low- and high-CSF Aβ 40 load. J. Neurochem.101,1053–1059 (2007).
  Medline CASGoogle Scholar
• 20  Wiltfang J, Esselmann H, Bibl M et al.: Highly conserved and disease-specific patterns of carboxyterminally truncated Aβ peptides 1–37/38/39 in addition to 1–40/42 in Alzheimer’s disease and in patients with chronic neuroinflammation. J. Neurochem.81,481–496 (2002).
  Medline CASGoogle Scholar
• 21  Bibl M, Mollenhauer B, Esselmann H et al.: CSF amyloid-β-peptides in Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease dementia. Brain129,1177–1187 (2006).
  MedlineGoogle Scholar
• 22  Bibl M, Mollenhauer B, Esselmann H et al.: CSF diagnosis of Alzheimer’s disease and dementia with Lewy bodies. J. Neural Transm.10, (2006).
  Google Scholar
• 23  Bibl M, Mollenhauer B, Lewczuk P et al.: Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias. Mol. Psychiatry12,671–680 (2007).
  Medline CASGoogle Scholar
• 24  Sunderland T, Linker G, Mirza N et al.: Decreased β-amyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer’s disease. JAMA289,2094–2103 (2003).
  MedlineGoogle Scholar
• 25  Craig-Schapiro R, Fagan A, Holtzman D: Biomarkers of Alzheimer’s disease. Neurobiol. Dis.35,128–140 (2009).
  Medline CASGoogle Scholar
• 26  Mattsson N, Zetterberg H, Hansson O et al.: CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA302,385–393 (2009).
  Medline CASGoogle Scholar
• 27  Tapiola T, Alafuzoff I, Herukka S et al.: Cerebrospinal fluid β-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch. Neurol.66,382–389 (2009).
  MedlineGoogle Scholar
• 28  Buerger K, Frisoni G, Uspenskaya O et al.: Validation of Alzheimer’s disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer’s Disease Neuroimaging Initiative (E-ADNI). Expl. Gerontol.44,579–585 (2009).
  Medline CASGoogle Scholar
• 29  Visser P, Verhey F, Knol D et al.: Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol.8,619–627 (2009).
  MedlineGoogle Scholar
• 30  Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol.2,605–613 (2003).
  Medline CASGoogle Scholar
• 31  Zhong Z, Ewers M, Teipel S et al.: Levels of b-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch. Gen. Psychiatry64,718–726 (2007).
  Medline CASGoogle Scholar
• 32  Ewers M, Zhong Z, Bürger K et al.: Increased CSF-BACE 1 activity is associated with APOE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer’s disease. Brain131,1252–1258 (2008).
  MedlineGoogle Scholar
• 33  Klunk W, Engler H, Nordberg A et al.: Imaging brain amyloid in Alzheimer’s disease with Pittsburgh compound-B. Ann. Neurol.55,306–319 (2004).▪▪Representing the first human study of amyloid-imaging PET tracer compound Pittsburgh Compound-B (PIB), this report describes retention of PIB in areas of AD brains known to contain amyloid, and additionally describes an inverse relationship between PIB PET signal and cerebral glucose metabolism, measured by FDG-PET.
  Medline CASGoogle Scholar
• 34  Fagan A, Mintun M, Mach R et al.: Inverse relation between in vivo amyloid imaging load and CSF Aβ₄₂ in humans. Ann. Neurol.59,512–519 (2006).▪▪ Illustrates an inverse relationship between mean cortical retention of amyloid-imaging PET tracer compound PIB and cerebrospinal fluid (CSF) Aβ42 levels among demented and nondemented subjects alike, suggesting that brain amyloid deposition results in low CSF Aβ42, and that amyloid imaging and CSF Aβ42 might serve as antecedent biomarkers of preclinical AD.
  Medline CASGoogle Scholar
• 35  Fagan A, Roe C, Xiong C, Mintun M, Morris J, Holtzman D: Cerebrospinal fluid tau/Aβ₄₂ ratio as a prediction of cognitive decline in nondemented older adults. Arch. Neurol.64,343–349 (2007).
  MedlineGoogle Scholar
• 36  Forsberg A, Engler H, Almkvist O et al.: PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol. Aging29,1456–1465 (2008).
  Medline CASGoogle Scholar
• 37  Koivunen J, Pirttilä T, Kemppainen N et al.: PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid β-amyloid in mild cognitive impairment. Dement. Geriatr. Cogn. Disord.26,378–383 (2008).
  Medline CASGoogle Scholar
• 38  Jagust W, Landau S, Shaw L et al.: Relationships between biomarkers in aging and dementia. Neurology73,1193–1199 (2009).
  Medline CASGoogle Scholar
• 39  Grimmer T, Riemenschneider M, Förstl H et al.: β amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol. Psychiatry65,927–934 (2009).
  Medline CASGoogle Scholar
• 40  Fagan A, Mintun M, Shah A et al.: Cerebrospinal fluid tau and p-tau181 increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol. Med.1,371–380 (2009).
  Medline CASGoogle Scholar
• 41  Aizenstein H, Nebes R, Saxton J et al.: Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch. Neurol.65,1509–1517 (2008).
  MedlineGoogle Scholar
• 42  Morris J, Roe C, Grant E et al.: Pittsburgh Compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Arch. Neurol.66(12),1469–1475 (2009).▪▪ Demonstrates that the presence of brain amyloid in cognitively normal individuals is not benign but rather is predictive of future cognitive decline.
  MedlineGoogle Scholar
• 43  Cairns N, Ikonomovic M, Benzinger T et al.: Absence of Pittsburgh Compound B detection of cerebral Amyloid β in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease. Arch. Neurol.66(12),1557–1562 (2009).
  MedlineGoogle Scholar
• 44  Itoh N, Arai H, Urakami K et al.: Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer’s disease. Ann. Neurol.50,150–156 (2001).
  Medline CASGoogle Scholar
• 45  Buerger K, Teipel S, Zinkowski R et al.: CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects. Neurology59,627–629 (2002).
  Medline CASGoogle Scholar
• 46  Hampel H, Mitchell A, Blennow K et al.: Core biological marker candidates of Alzheimer’s disease – perspectives for diagnosis, prediction of outcome and reflection of biological activity. J. Neural. Transm.111,247–272 (2004).
  Medline CASGoogle Scholar
• 47  Buerger K, Ewers M, Pirttila T et al.: CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain129(Pt 11),3035–3041 (2006).
  MedlineGoogle Scholar
• 48  Ost M, Nylén K, Csajbok L et al.: Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injuries. Neurology67,1600–1604 (2006).
  Medline CASGoogle Scholar
• 49  Blennow K, Nellgård B: Amyloid β 1–42 and tau in cerebrospinal fluid after severe traumatic brain injury. Neurology62,159 (2004).
  MedlineGoogle Scholar
• 50  Yao C, Williams A, Ottens A et al.: Detection of protein biomarkers using high-throughput immunoblotting following focal ischemic or penetrating ballistic-like brain injuries in rats. Brain Inj.22,723–732 (2008).
  MedlineGoogle Scholar
• 51  Zetterberg H, Pedersen M, Lind K et al.: Intra-individual stability of CSF biomarkers for Alzheimer’s disease over two years. J. Alzheimers Dis.12,255–260 (2007).
  Medline CASGoogle Scholar
• 52  Blennow K, Zetterberg H, Minthon L et al.: Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci. Lett.419,18–22 (2007).
  Medline CASGoogle Scholar
• 53  Terry RD, Masliah E, Salmon DP et al.: Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol.30,572–580 (1991).
  Medline CASGoogle Scholar
• 54  Fagan A, Head D, Shah A et al.: Decreased cerebrospinal fluid Aβ₄₂ correlates with brain atrophy in cognitively normal elderly. Ann. Neurol.65,175–183 (2009).
  Google Scholar
• 55  Fukuyama R, Mizuno T, Mizuno T et al.: Age-dependent changes in the levels of Aβ₄₀ and Aβ₄₂ in cerebrospinal fluid from control subjects, and a decrease in the ratio of Aβ₄₂ to Aβ₄₀ level in cerebrospinal fluid from Alzheimer’s disease patients. Eur. Neurol.43,155–160 (2000).
  Medline CASGoogle Scholar
• 56  Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM: Plasma and cerebrospinal fluid levels of Amyloid β proteins 1–40 and 1–42 in Alzheimer’s disease. Arch. Neurol.57,100–105 (2000).
  Medline CASGoogle Scholar
• 57  Lewczuk P, Esselmann H, Otto M et al.: Neurochemical diagnosis of Alzheimer’s dementia by CSF Aβ₄₂, Aβ₄₂/Aβ₄₀ ratio and total tau. Neurobiol. Aging25,273–281 (2004).
  Medline CASGoogle Scholar
• 58  Hansson O, Zetterberg H, Buchhave P et al.: Prediction of Alzheimer’s disease using the CSF Aβ₄₂/Aβ₄₀ ratio in patients with mild cognitive impairment. Dement. Geriatr. Cogn. Disord.23,316–320 (2007).
  Medline CASGoogle Scholar
• 59  Welge V, Fiege O, Lewczuk P et al.: Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease. J. Neural. Transm.116,203–212 (2009).
  Medline CASGoogle Scholar
• 60  Lewczuk P, Kornhuber J, Vanderstichele H et al.: Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: A multicenter study. Neurobiol. Aging29,812–818 (2008).
  Medline CASGoogle Scholar
• 61  Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol.5,228–234 (2006).▪ First report to demonstrate the utility of CSF biomarkers Aβ42, tau and phospho-tau to predict progression of patients from mild cognitive impairment to dementia attributed clinically to AD.
  Medline CASGoogle Scholar
• 62  Snider B, Fagan A, Roe C et al.: Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. Arch. Neurol.66,638–645 (2009).▪ First study to correlate CSF biomarkers with the rate of future cognitive decline in individuals diagnosed with very early stage dementia.
  MedlineGoogle Scholar
• 63  Li G, Sokal I, Quinn J et al.: CSF tau/Aβ₄₂ ratio for increased risk of mild cognitive impairment: a follow-up study. Neurology69,631–639 (2007).
  Medline CASGoogle Scholar
• 64  Zhang J, Goodlett D, Quinn J et al.: Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer’s disease. J. Alzheimers Dis.7,125–133 (2005).
  Medline CASGoogle Scholar
• 65  Hu Y, Hosseini A, Kauwe J et al.: Identification and validation of novel CSF biomarkers for early stages of Alzheimer’s disease. Proteomics Clin. Appl.1,1373–1384 (2007).
  Medline CASGoogle Scholar
• 66  Castano E, Roher A, Esh C, Kokjohn T, Beach T: Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer’s disease and non-demented elderly subjects. Neurol. Res.28,155–163 (2006).
  Medline CASGoogle Scholar
• 67  Finehout E, Franck Z, Choe L, Relkin N, Lee K: Cerebrospinal fluid proteomic biomarkers for Alzheimer’s disease. Ann. Neurol.61,120–129 (2006).
  Google Scholar
• 68  Archer H, Edison P, Brooks D et al.: Amyloid load and cerebral atrophy in Alzheimer’s disease: an 11C-PIB positron emission tomography study. Ann. Neurol.60,145–147 (2006).
  MedlineGoogle Scholar
• 69  De Leon Mj, Desanti S, Zinkowski R et al.: Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol. Aging27(3),394–401 (2006).
  Medline CASGoogle Scholar
• 70  Hampel H, Burger K, Pruessner J et al.: Correlation of cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 with rates of hippocampal atrophy in Alzheimer disease. Arch. Neurol.62,770–773 (2005).▪ Demonstrates that levels of CSF ptau231 can predict progression of hippocampal atrophy in AD, providing a good example of the power of combining biomarker modalities.
  MedlineGoogle Scholar
• 71  De Leon M, Mosconi L, Li J et al.: Longitudinal CSF isoprostane and MRI atrophy in the progression to AD. J. Neurol. Sci.254(12),1666–1675 (2007).
  CASGoogle Scholar
• 72  Kauwe J, Cruchaga C, Mayo K et al.: Variation in MAPT is associated with cerebrospinal fluid tau levels in the presence of amyloid-β deposition. Proc. Natl Acad. Sci. USA105,8050–8054 (2008).▪ Demonstrates that CSF biomarkers can be used as endophenotypes for genetic studies of AD by providing evidence for a genetic–epigenetic interaction that predisposes some individuals to the development of tauopathy and accelerated AD progression.
  Medline CASGoogle Scholar
• 73  Kauwe J, Wang J, Mayo K et al.: Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid β. Neurogenetics10,13–17 (2009).
  Medline CASGoogle Scholar
• 74  Bateman R, Munsell L, Morris J, Swarm R, Yarasheski K, Holtzman D: Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med.12,856–861 (2006).▪ This elegant study describes a novel method to measure the production and clearance rates of CNS proteins in living humans and demonstrated a very fast turnover of Aβ in young (23-45 years) cognitively normal individuals.
  Medline CASGoogle Scholar
• 75  Bateman R, Siemers E, Mawuenyega K et al.: A γ-secretase inhibitor decreases amyloid-β production in the central nervous system. Ann. Neurol.66,48–54 (2009).▪▪ This study demonstrates the utility of an in vivo labeling method to test the effect of a drug on the pharmacokinetics of CNS protein (in this case the Aβ peptide) production and clearance in living humans.
  Medline CASGoogle Scholar
• 76  Lewczuk P, Beck G, Esselmann H et al.: Effect of sample collection tubes on cerebrospinal fluid concentrations of tau proteins and amyloid β peptides. Clin. Chem.52,332–334 (2006).
  Medline CASGoogle Scholar
• 77  Peskind E, Nordberg A, Darreh-Shori T, Soininen H: Safety of lumbar puncture procedures in patients with Alzheimer’s disease. Curr. Alzheimer Res.6,290–292 (2009).
  Medline CASGoogle Scholar
• 78  Mueller S, Weiner M, Thal L et al.: Ways toward an early diagnosis in Alzheimer’s disease: the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimers Dement.1,55–66 (2005).▪ Introduces the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the first large-scale, multi-institutional study of its kind designed to obtain longitudinal biomarker and clinical data from individuals with mild cognitive impairment, AD and cognitively normal individuals.
  MedlineGoogle Scholar
• 79  Frisoni G, Henneman W, Weiner M et al.: The pilot European Alzheimer’s Disease Neuroimaging Initiative of the European Alzheimer’s Disease Consortium. Alzheimers Dement.4,255–264 (2008).
  MedlineGoogle Scholar
• 80  Ihara Y: Overview on Alzheimer’s disease. Rinsho Shinkeigaku47,902–904 (2007).
  MedlineGoogle Scholar
• 81  Coats M, Morris J: Antecedent biomarkers of Alzheimer’s disease: The Adult Children Study. J. Geriatr. Psychiatry Neurol.18,242–244 (2005).
  MedlineGoogle Scholar
• 82  Kornhuber J, Schmidtke K, Frolich L et al.: Early and differential diagnosis of dementia and mild cognitive impairment: design and cohort baseline characteristics of the German Dementia Competence Network. Dement. Geriatr. Cogn. Disord.27,404–417 (2009).
  MedlineGoogle Scholar
• 83  Perrin RJ, Fagan AM, Holtzman DM: Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature461(7266),916–922 (2009).
  Medline CASGoogle Scholar
• 84  Fagan AM, Mintun MA, Shah AR et al.: Cerebrospinal fluid tau and p-tau181 increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol. Med.1(8–9),371–380 (2009).
  Medline CASGoogle Scholar
• 85  Bateman RJ, Siemers ER, Mawuenyega KG et al.: A γ-secretase inhibitor decreases amyloid-β production in the central nervous system. Ann. Neurol.66,48–54 (2009).
  Medline CASGoogle Scholar
• 101  Alzheimer’s Association. www.alz.org
  Google Scholar
• 102  Dominantly Inherited Alzheimer Network (DIAN). www.dian-info.org
  Google Scholar