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Amyloid-β and τ biomarkers in Parkinson's disease–dementia

      Abstract

      Dementia is a frequent and devastating non-motor complication of advanced Parkinson's disease (PD). There is growing evidence of a synergistic role of Alzheimer's-type brain lesions containing τ and amyloid-β (Aβ) proteins and cortical Lewy aggregates in PD-related dementia (PDD). Therefore, biomarkers of both τ and Aβ may be seen as diagnostic and predictive markers of PDD. Here, we review the available studies in PD and PDD using cerebrospinal fluid (CSF) total τ, phospho-τ, and/or Aβ levels, and PET probes targeting Alzheimer's-type lesions. Overall, high CSF τ and phospho-τ levels and/or low CSF Aβ levels have been found in part of PDD patients, and a longitudinal study has found greater worsening in cognitive performance over time in non-demented PD patients with low baseline CSF Aβ levels. Few studies are available on the use of PET imaging in PD, all of them using the Pittsburgh B compound (PIB), and with figures of about 30% of scans with PIB uptake in the AD-range in PDD. We conclude that these CSF and PET markers deserve further evaluation as candidate biomarkers of dementia in PD. According to this, we are currently undertaking a longitudinal project on the predictive value of dementia of the combined use of CSF τ and Aβ and 18F-FDDNP PET in PD.

      Keywords

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      References

        • Emre M.
        • Aarsland D.
        • Brown R.
        • Burn D.J.
        • Duyckaerts C.
        • Mizuno Y.
        • et al.
        Clinical diagnostic criteria for dementia associated with Parkinson's disease.
        Mov Disord. 2007; 22: 1689-1707
        • Dubois B.
        • Ruberg M.
        • Javoy-Agid F.
        • Ploska A.
        • Agid Y.
        A subcortico–cortical cholinergic system is affected in Parkinson's disease.
        Brain Res. 1983; 288: 213-218
        • Aarsland D.
        • Perry R.
        • Brown A.
        • Larsen J.P.
        • Ballard C.
        Neuropathology of dementia in Parkinson's disease: a prospective, community-based study.
        Ann Neurol. 2005; 58: 773-776
        • Masliah E.
        • Rockenstein E.
        • Veinbergs I.
        • Sagara Y.
        • Mallory M.
        • Hashimoto M.
        • et al.
        Beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.
        Proc Natl Acad Sci USA. 2001; 98: 12245-12250
        • Clinton L.K.
        • Blurton-Jones M.
        • Myczek K.
        • Trojanowski J.Q.
        • Lamerla F.M.
        Synergistic interactions between Aβ, tau, and α-synuclein: acceleration of neuropathology and cognitive decline.
        J Neuroscience. 2010; 30: 7281-7289
        • Sabbagh M.N.
        • Adler C.H.
        • Lahti T.J.
        • Connor D.J.
        • Vedders L.
        • Peterson L.K.
        • et al.
        Parkinson disease with dementia: comparing patients with and without Alzheimer pathology.
        Alzheimer Dis Assoc Disord. 2009; 23: 295-297
        • Braak H.
        • Braak E.
        Frequency of stages of Alzheimer-related lesions in different age categories.
        Neurobiol Aging. 1997; 18: 351-357
        • Lashley T.
        • Holton J.L.
        • Gray E.
        • Kirkham K.
        • O'Sullivan S.S.
        • Hilbig A.
        • et al.
        Cortical alpha-synuclein load is associated with amyloid-beta plaque burden in a subset of Parkinson's disease patients.
        Acta Neuropathol. 2008; 115: 417-425
        • Compta Y.
        • Parkkinen L.
        • O'Sullivan S.S.
        • Vandrovcova J.
        • Holton J.L.
        • Collins C.
        • et al.
        Lewy and Alzheimer's type pathologies in Parkinson's disease dementia: which is more important?.
        Brain. 2011; 134: 1493-1505
        • Halliday G.
        • Hely M.
        • Reid W.
        • Morris J.
        The progression of pathology in longitudinally followed patients with Parkinson's disease.
        Acta Neuropathol. 2008; 115: 409-415
        • Kalaitzakis M.E.
        • Graeber M.B.
        • Gentleman S.M.
        • Pearce R.K.B.
        Striatal beta-amyloid deposition in Parkinson disease with dementia.
        J Neuropathol Exp Neurol. 2008; 67: 155-161
        • Dubois B.
        • Feldman H.H.
        • Jacova C.
        • Dekosky S.T.
        • Barberger-Gateau P.
        • Cummings J.
        • et al.
        Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria.
        Lancet Neurol. 2007; 6: 734-746
        • Dubois B.
        • Feldman H.H.
        • Jacova C.
        • Cummings J.L.
        • Dekosky S.T.
        • Barberger-Gateau P.
        • et al.
        Revising the definition of Alzheimer's disease: a new lexicon.
        Lancet Neurol. 2010; 9: 1118-1127
        • Fagan A.M.
        • Mintun M.A.
        • Mach R.H.
        • Lee S.Y.
        • Dence C.S.
        • Shah A.R.
        • et al.
        Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans.
        Ann Neurol. 2006; 59: 512-519
        • Shaw L.M.
        • Vanderstichele H.
        • Knapik-Czajka M.
        • Clark C.M.
        • Aisen P.S.
        • Petersen R.C.
        • et al.
        Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
        Ann Neurol. 2009; 65: 403-413
        • Sjögren M.
        • Minthon L.
        • Davidsson P.
        • Granérus A.-K.
        • Clarberg A.
        • Vanderstichele H.
        • et al.
        CSF levels of tau, beta-amyloid(1–42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging.
        J Neural Transm. 2000; 107: 563-579
        • Kahle P.J.
        • Jakowec M.
        • Teipel S.J.
        • Hampel H.
        • Petzinger G.M.
        • Di Monte D.A.
        • et al.
        Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF.
        Neurology. 2000; 54: 1498-1504
        • Paraskevas G.P.
        • Kapaki E.
        • Liappas I.
        • Theotoka I.
        • Mamali I.
        • Zournas C.
        • et al.
        The diagnostic value of cerebrospinal fluid tau protein in dementing and nondementing neuropsychiatric disorders.
        J Geriatr Psychiatry Neurol. 2005; 18: 163-173
        • Molina J.A.
        • Benito-León J.
        • Jiménez-Jiménez F.J.
        • Ortí-Pareja M.
        • Berbel A.
        • Tallón-Barranco A.
        • et al.
        Tau protein concentrations in cerebrospinal fluid of non-demented Parkinson's disease patients.
        Neurosci Lett. 1997; 238: 139-141
        • Jansen S.E.
        • Vermes I.
        • de Vos R.A.
        Cerebrospinal-fluid tau protein and aspartate aminotransferase in Parkinson's disease.
        Lancet. 1998; 351: 1105-1106
        • Mollenhauer B.
        • Trenkwalder C.
        • von Ahsen N.
        • Bibl M.
        • Steinacker P.
        • Brechlin P.
        • et al.
        Beta-amlyoid 1–42 and tau-protein in cerebrospinal fluid of patients with Parkinson's disease dementia.
        Dement Geriatr Cogn Disord. 2006; 22: 200-208
        • Parnetti L.
        • Tiraboschi P.
        • Lanari A.
        • Peducci M.
        • Padiglioni C.
        • D'Amore C.
        • et al.
        Cerebrospinal fluid biomarkers in Parkinson's disease with dementia and dementia with Lewy bodies.
        Biol Psychiatry. 2008; 64: 850-855
        • Compta Y.
        • Martí M.J.
        • Ibarretxe-Bilbao N.
        • Junqué C.
        • Valldeoriola F.
        • Muñoz E.
        • et al.
        Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinson's disease.
        Mov Disord. 2009; 24: 2203-2210
        • Compta Y.
        • Ibarretxe-Bilbao N.
        • Junque C.
        • Bargallo N.
        • Braga-Pereira J.
        • Valldeoriola F.
        • et al.
        Tau and phospho-tau cerebrospinal levels correlate with temporal and frontal gray matter reduction in Parkinson's disease and Parkinson's disease with dementia.
        Mov Disord. 2009; 24: S295
        • Alves G.
        • Brønnick K.
        • Aarsland D.
        • Blennow K.
        • Zetterberg H.
        • Ballard C.
        • et al.
        CSF amyloid-beta and tau proteins, and cognitive performance, in early and untreated Parkinson's disease: the Norwegian ParkWest study.
        J Neurol Neurosurg Psychiatry. 2010; 81: 1080-1086
        • Siderowf A.
        • Xie S.X.
        • Hurtig H.
        • Weintraub D.
        • Duda J.
        • Chen-Plotkin A.
        • et al.
        CSF amyloid β1–42 predicts cognitive decline in Parkinson disease.
        Neurology. 2010; 75: 1055-1061
        • Montine T.J.
        • Shi M.
        • Quinn J.F.
        • Peskind E.R.
        • Craft S.
        • Ginghina C.
        • et al.
        CSF Aβ(42) and tau in Parkinson's disease with cognitive impairment.
        Mov Disord. 2010; 25: 2682-2685
        • Přikrylová Vranová H.
        • Mareš J.
        • Nevrlý M.
        • Stejskal D.
        • Zapletalová J.
        • Hluštík P.
        • et al.
        CSF markers of neurodegeneration in Parkinson's disease.
        J Neural Transm. 2010; 117: 1177-1181
        • Compta Y.
        • Ezquerra M.
        • Muñoz E.
        • Tolosa E.
        • Valldeoriola F.
        • Rios J.
        • et al.
        High cerebrospinal tau levels are associated with the rs242557 tau gene variant and low cerebrospinal β-amyloid in Parkinson disease.
        Neurosci Lett. 2011; 487: 169-173
        • Leverenz J.B.
        • Watson G.S.
        • Shofer J.
        • Zabetian C.P.
        • Zhang J.
        • Montine T.J.
        Cerebrospinal fluid biomarkers and cognitive performance in non-demented patients with Parkinson's disease.
        Parkinsonism Relat Disord. 2011; 17: 61-64
        • Jack Jr., C.R.
        • Dickson D.W.
        • Parisi J.E.
        • Xu Y.C.
        • Cha R.H.
        • O'Brien P.C.
        • et al.
        Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.
        Neurology. 2002; 58: 750-757
        • Kauwe J.S.
        • Cruchaga C.
        • Mayo K.
        • Fenoglio C.
        • Bertelsen S.
        • Nowotny P.
        • et al.
        Variation in TAU is associated with cerebrospinal fluid tau levels in the presence of amyloid-beta deposition.
        Proc Natl Acad Sci U S A. 2008; 105: 8050-8054
        • Holmberg B.
        • Johnels B.
        • Blennow K.
        • Rosengren L.
        Cerebrospinal fluid Aβ 42 is reduced in multiple system atrophy but normal in Parkinson's disease and progressive supranuclear palsy.
        Mov Disord. 2003; 18: 186-190
        • Mollenhauer B.
        • Bibl M.
        • Esselmann H.
        • Steinacker P.
        • Trenkwalder C.
        • Wiltfang J.
        • et al.
        Tauopathies and synucleinopathies: do cerebrospinal fluid beta-amyloid peptides reflect disease-specific pathogenesis?.
        J Neural Transm. 2007; 114: 919-927
        • Bibl M.
        • Mollenhauer B.
        • Esselmann H.
        • Lewczuk P.
        • Klafki H.W.
        • Sparbier K.
        • et al.
        CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia.
        Brain. 2006; 129: 1177-1187
        • Mathis C.A.
        • Wang Y.
        • Holt D.P.
        • Huang G.F.
        • Debnath M.L.
        • Klunk W.E.
        Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents.
        J Med Chem. 2003; 46: 2740-2754
        • Agdeppa E.D.
        • Kepe V.
        • Liu J.
        • Flores-Torres S.
        • Satyamurthy N.
        • Petric A.
        • et al.
        Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease.
        J Neurosci. 2001; 21: RC189
        • Ikonomovic M.D.
        • Klunk W.E.
        • Abrahamson E.E.
        • Mathis C.A.
        • Price J.C.
        • Tsopelas N.D.
        • et al.
        Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease.
        Brain. 2008; 131: 1630-1645
        • Small G.W.
        • Kepe V.
        • Ercoli L.M.
        • Siddarth P.
        • Bookheimer S.Y.
        • Miller K.J.
        • et al.
        PET of brain amyloid and tau in mild cognitive impairment.
        N Engl J Med. 2006; 355: 2652-2663
        • Tolboom N.
        • Yaqub M.
        • van der Flier W.M.
        • Boellaard R.
        • Luurtsema G.
        • Windhorst A.D.
        • et al.
        Detection of Alzheimer Pathology In Vivo Using Both 11C-PIB and 18F-FDDNP PET.
        J Nucl Med. 2009; 50: 191-197
        • Shin J.
        • Lee S.Y.
        • Kim S.H.
        • Kim Y.B.
        • Cho S.J.
        Multitracer PET imaging of amyloid plaques and neurofibrillary tangles in Alzheimer's disease.
        Neuroimage. 2008; 43: 236-244
        • Johansson A.
        • Savitcheva I.
        • Forsberg A.
        • Engler H.
        • Långström B.
        • Nordberg A.
        • et al.
        [(11)C]-PIB imaging in patients with Parkinson's disease: preliminary results.
        Parkinsonism Relat Disord. 2008; 14: 345-347
        • Maetzler W.
        • Reimold M.
        • Liepelt I.
        • Solbach C.
        • Leyhe T.
        • Schweitzer K.
        • et al.
        [11C]PIB binding in Parkinson's disease dementia.
        Neuroimage. 2008; 39: 1027-1033
        • Edison P.
        • Rowe C.C.
        • Rinne J.O.
        • Ng S.
        • Ahmed I.
        • Kemppainen N.
        • et al.
        Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography.
        J Neurol Neurosurg Psychiatry. 2008; 79: 1331-1338
        • Gomperts S.N.
        • Rentz D.M.
        • Moran E.
        • Becker J.A.
        • Locascio J.J.
        • Klunk W.E.
        • et al.
        Imaging amyloid deposition in Lewy body diseases.
        Neurology. 2008; 71: 903-910
        • Maetzler W.
        • Liepelt I.
        • Reimold M.
        • Reischl G.
        • Solbach C.
        • Becker C.
        • et al.
        Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics.
        Neurobiol Dis. 2009; 34: 107-112
        • Foster E.R.
        • Campbell M.C.
        • Burack M.A.
        • Hartlein J.
        • Flores H.P.
        • Cairns N.J.
        • et al.
        Amyloid imaging of Lewy body-associated disorders.
        Mov Disord. 2010; 25: 2516-2523
        • Jokinen P.
        • Scheinin N.
        • Aalto S.
        • Någren K.
        • Savisto N.
        • Parkkola R.
        • et al.
        [(11)C]PIB-, [(18)F]FDG-PET and MRI imaging in patients with Parkinson's disease with and without dementia.
        Parkinsonism Relat Disord. 2010; 16: 666-670
        • Burack M.A.
        • Hartlein J.
        • Flores H.P.
        • Taylor-Reinwald L.
        • Perlmutter J.S.
        • Cairns N.J.
        In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia.
        Neurology. 2010; 74: 77-84
        • Kalaitzakis M.E.
        • Walls A.J.
        • Pearce R.K.
        • Gentleman S.M.
        Striatal Aβ peptide deposition mirrors dementia and differentiates DLB and PDD from other Parkinsonian syndromes.
        Neurobiol Dis. 2011; 41: 377-384