Abstract
Very little data exist to evaluate the value of longitudinal CSF biological markers for Alzheimer's disease (AD).Most studies indicate that tau and amyloid beta markers do not reflect disease progression. We now report on a longitudinal, three-time point, CSF Isoprostane (IsoP) and quantitative MRI study that examined 11 normal elderly (NL) volunteers and 6 Mild Cognitive Impairment (MCI) patients. After 4 years, all 6 MCI patients declined to AD and 2 of the NL subjects declined to MCI. At baseline and longitudinally, the MCI patients showed reduced delayed memory, increased IsoP levels, and reduced medial temporal lobe gray matter concentrations as compared to NL. A group comprised of all decliners to AD or to MCI (n = 8) was distinguished at baseline from the stable NL controls (n = 9) by IsoP with 100% accuracy.Moreover, both at baseline and longitudinally, the IsoP measures significantly improved the diagnostic and predictive outcomes of conventional memory testing and quantitative MRI measurements. These data indicate that IsoP is potentially useful for both the early detection of AD-related pathology and for monitoring the course of AD.
Similar content being viewed by others
References
Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L (2006) Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. The Lancet Neurology 5:228–234
Andreasen N, Minthon L, Vanmechelen E (1999) Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment. Neurosci Lett 273:5–8
Riemenschneider M, Lautenschlager N, Wagenpfeil S, Diehl J, Drzezga A, Kurz A (2002) Cerebrospinal fluid tau and B-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. Arch Neurol 59:1729–1734
Hampel H, Teipel SJ, Fuchsberger T, Andreasen N, Wiltfang J, Otto M, Shen Y, Dodel R, Du Y, Farlow, et al. (2004) Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Mol Psychiatry 9:705–710
Herukka SK, Hallikainen M, Soininen H, Pirttila T (2005) CSF Aβ42 and tau or phosphorylated tau and prediction of progressive mild cognitive impairment. Neurol 64:1294–1297
Arai H, Ishiguro K, Ohna H, Moriyama M, Itoh N, Okamura N, Matsui T, Morikawa Y, Horikawa E, Imahori K (2000) CSF phosphorylated tau protein and mild cognitive impairment: A prospective study. Exp Neurol 166:201–203
Buerger K, Teipel SJ, Zinkowski R, Blennow K, Arai H, Engel R, Hofmann- Kiefer K, McCulloch C, Ptok U, Heun R, Andreasen N, DeBernardis J, Kerkman D, Moeller HJ, Davies P, Hampel H (2002) CSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects. Neurol 59:627–629
Brys M, Mosconi L, De Santi S, Rich KE, de Leon MJ (2006) CSF Biomarkers for Mild Cognitive Impairment. Aging Health 2:111–121
Glodzik-Sobanska L, Rusinek H, Mosconi L, Li Y, Zhan J, De Santi S, Convit A, Rich KE, Brys M, de Leon MJ (2005) The role of quantitative structural imaging in the early diagnosis of Alzheimer's disease. Neuroimaging Clinics of North America 15:803–826
de Leon MJ, Klunk WE (2006) Biomarkers for the early diagnosis of Alzheimer's disease. The Lancet Neurology 5:198–199
Hampel H, Buerger K, Kohnken R, Teipel SJ, Zinkowski R, Moeller HJ, Rapoport SI, Davies P (2001) Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Ann Neurol 49:545–546
de Leon MJ, Segal CY, Tarshish CY, De Santi S, Zinkowski R, Mehta PD, Convit A, Caraos C, Rusinek H, Tsui W, Saint- Louis LA, DeBernardis J, Kerkman D, Qadri F, Gary A, Lesbre P, Wisniewski H, Poirier J, Davies P (2002) Longitudinal CSF tau load increases in mild cognitive impairment. Neurosci Lett 333:183–186
Montine TJ, Neely MD, Quinn JF, Beal MF, Markesbery WR, Roberts LJ, Morrow JD (2002) Lipid peroxidation in aging brain and Alzheimer's disease. Free Radic Biol Med 33:620–626
de Leon MJ, De Santi S, Zinkowski R, Mehta PD, Pratico D, Segal S, Rusinek H, Li J, Tsui W, Saint Louis LA, et al. (2006) Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol Aging 27:394–401
Quinn JF, Montine KS, Moore M, Morrow JD, Kaye JA, Montine TJ (2004) Suppression of longitudinal increase in CSF F_2-isoprostanes in Alzheimer's disease. J Alz Dis 6:93–97
Reisberg B, Ferris SH, de Leon MJ, Crook T (1982) The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiat 139:1136–1139
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurol 34:939–944
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Washington, D. C. : American Psychiatric Association
Pratico D, Clark CM, Lee VM, Trojanowski JQ, Rokach J, Fitzgerald GA (2000) Increased 8, 12-iso-iPF2alpha- VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Ann Neurol 48:809–812
Kluger A, Ferris SH, Golomb J, Mittelman, MS, Reisberg B (1999) Neuropsychological prediction of decline to dementia in nondemented elderly. J Geriat Psychiat Neurol 12:168–179
De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Boppana M, Tsui WH, Daisley K, Wang GJ, Schlyer D (2001) Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 22:529–539
Ashburner J, Friston KJ (2000) Voxelbased morphometry – the methods. Neuroimage 11:805–821
Good CD, Scahill RI, Fox NC, Ashburner J, Friston KJ, Chan D, Crum WR, Rossor MN, Frackowiak RSJ (2002) Automatic differentiation of anatomical patterns in the human brain: validation with studies of degenerative dementias. Neuroimage 17:29–46
Talairach J, Tournoux P (1988) Co- Planar stereotaxic atlas of the human brain. Stuttgart: Thieme
Friston KJ, Holmes AP, Worsley KJ, Poline J-P, Frith CD, Frackowiak RSJ (1995) Statistical parametric maps in functional imaging: A general linear approach. Human Brain Mapping 2:189–210
Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RSJ (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14:21–36
Friston KJ, Frith CD, Liddle PF, Frackowiak RSJ (1991) Comparing functional (PET) images: the assessment of significant change. Journal of Cerebral Blood Flow and Metabolism 11:690–699
Friston K, Ashburner J, Frith C, Poline J-B, Heather J, Frackowiak R (1995) Spatial registration and normalization of images. Hum Brain Mapp 3:165–189
Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE (1995) A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of Fluorine-18- FDG PET. The J Nucl Med 36(7):1238–1248
Diggle PJ, Heagerty P, Liang K-Y, Zeger SC (2002) Analysis of Longitudinal Data. New York: Oxford University Press
Friston KJ, Stephan KE, Lund TE, Morcom A, Kiebel SJ (2004) Mixedeffects and fMRI studies. Neuroimage 24:244–252
Montine TJ, Beal MF, Cudkowicz ME, O'Donnell H, Margolin RA, McFarland L, Bachrach AF, Zackert WE, Roberts LJ, Morrow, et al. (1999) Increased CSF F2-isoprostane concentration in probable AD. Neurol 52:562–565
Pratico D, Clark CM, Liun F, Lee VY, Trojanowski JQ (2002) Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 59:972–976
Markesbery WR, Kryscio RJ, Lovell MA, Morrow JD (2005) Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann Neurol 58(5):730–735
Rusinek H, De Santi S, Frid D, Tsui W, Tarshish C, Convit A, de Leon MJ (2003) Regional brain atrophy rate predicts future cognitive decline: 6- year longitudinal MR imaging study of normal aging. Radiology 229:691–696
den Heijer T, Geerlings MI, Hoebeek FE, Hofman A, Koudstaal PJ, Breteler M (2006) Use of hippocampal and amygdalar volumes on magnetic resonance imaging to predict dementia in cognitively intact elderly people. Arch Gen Psychiat 63:57–62
Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278:412–419
Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EKM, Jones PKP, Ghanbari HA, Wataya AT, Shimohama S, Chiba S, Atwood C, Petersen RBP, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767
Pratico D, Uryu K, Leight S, Trojanowski JQ, Lee VMY (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21:4183–4187
Matsuoka Y, Picciano M, La Francois J, Duff K (2001) Fibrillar (beta)-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer's disease. Neurosci 104:609–613
Buerger K, Zinkowski R, Teipel SJ, Tapiola T, Arai H, Blennow K, Andreasen N, Hofmann-Kiefer K, DeBernardis J, Kerkman D, McCulloch C, Kohnken R, Padberg F, Pirttila T, Schapiro M, Rapoport S, Moller HJ, Davies P, Hampel H (2002) Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 59:1267–1272
Buerger K, Zinkowski R, Teipel SJ, Arai H, DeBernardis J, Kerkman D, McCulloch C, Padberg F, Faltraco F, Goernitz A, Tapiola T, Rapoport SI, Pirttila T, Moller HJ, Hampel H (2003) Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Am J Psychiat 160:376–379
Buerger K, Otto M, Teipel SJ, Zinkowski R, Blennow K, DeBernardis J, Kerkman D, Schroder J, Schonknecht P, Cepek L (2006) Dissociation between CSF total tau and tau protein phosphorylated at threonine 231 in Creutzfeldt-Jakob disease. Neurobiol Aging 27:10–15
Arai H, Morikawa Y, Higuchi M, Matsui T, Clark CM, Miura M, Machida N, Lee VM, Trojanowski JQ, Sasaki H (1997) Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology. Biochem Biophys Res Commun 236:262–264
Mollenhauer B, Bibl M, Trenkwalder C, Stiens G, Cepek L, Steinacker P, Ciesielczyk B, Neubert K, Wiltfang J, Kretzschmar HA, Poser S, Otto M (2005) Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease. J Neural Transm 112:933–948
Yao Y, Zhukareva V, Sung S, Clark CM, Rokach J, Lee VMY, Trojanowski JQ, Pratico D (2003) Enhanced brain levels of 8, 12-iso-iPF2-VI differentiate AD from frontotemporal dementia. Neurol 61:475–478
Montine TJ, Kaye JA, Montine KS, McFarland L, Morrow JD, Quinn JF (2001) Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls. Arch Pathol Lab Med 125:510–512
Lin CL, Hsu YT, Lin TK, Morrow JD, Hsu JC, Hsu YH, Hsieh TC, Tsay PK, Yen HC (2006) Increased levels of F2- isoprostanes following aneurysmal subarachnoid hemorrhage in humans. Free Radic Biol Med 40:1466–1473
Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 23:298–304
De Caterina R, Cipollone F, Filardo FP, Zimarino M, Bernini W, Lazzerini G, Bucciarelli T, Falco A, Marchesani P, Muraro R, Mezzetti A, Ciabattoni G (2002) Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2-isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E. Circulation 106:2543–2549
Pratico D, Lawson JA, Rokach J, Fitzgerald GA (2001) The isoprostanes in biology and medicine. Trends in Endocrinology and Metabolism 12:243–247
Ding T, Yao Y, Pratico D (2005) Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models. Neurochemistry International 46:435–439
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
de Leon, M.J., Mosconi, L., Li, J. et al. Longitudinal CSF isoprostane and MRI atrophy in the progression to AD. J Neurol 254, 1666–1675 (2007). https://doi.org/10.1007/s00415-007-0610-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-007-0610-z