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CSF diagnosis of Alzheimer’s disease and dementia with Lewy bodies

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Summary.

Differential diagnosis of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) is often crucial. CSF Tau protein and Amyloid-beta (Aβ) peptides have shown diagnostic value for the diagnosis of AD, but discrimination from DLB was poor.

Herein, we investigate CSF of 18 patients with probable AD, 25 with probable DLB and 14 non-demented disease controls (NDC) by Aβ-SDS-PAGE/immunoblot and commercially available ELISAs for Aβ1-42 and tau. CSF Aβ peptide patterns and tau exhibited disease specific alterations among AD and DLB. The ratio of Aβ1-42 to Aβ1-38 and Aβ1-42 to Aβ1-37, respectively, in combination with absolute tau, yielded a sensitivity and specificity of 100 and 92%, respectively. We conclude that CSF Aβ peptide patterns and tau levels reflect disease-specific pathophysiological pathways of these dementias as distinct neurochemical phenotypes. Combined evaluation of these biomarkers provides a reasonable accuracy for differential diagnosis of AD and DLB.

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Abbreviations

Aβ peptides:

amyloid-beta peptides

Aβ-SDS-PAGE/immunoblot:

amyloid-beta-sodium-dodecyl-sulphate-polyacrylamide-gel-electrophoresis with western immunoblot

AD:

Alzheimer’s disease

ApoE ɛ4:

apolipoprotein E allele ɛ4

APP:

beta-amyloid precursor protein

bicine:

N,N′-bis-[2-hydroxyethyl]glycine

CCD-camera:

charge coupled device camera

CSF:

cerebrospinal fluid

Ct-elongated:

carboxyterminally elongated

Ct-truncated:

carboxyterminally truncated

DLB:

dementia with Lewy bodies

ECL:

enhanced chemiluminescence

ELISA:

Enzyme Linked Immunosorbent Assay

MMSE:

Mini-Mental-Status Examination

NINCDS-ADRDA:

National Institute Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association

ND:

non-demented

PDD:

Parkinson’s disease dementia

PVDF:

polyvinylidene difluoride

SDS:

sodium dodecyl sulphate

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Authors and Affiliations

  1. Department of Psychiatry, University of Goettingen, Goettingen, Germany

    M. Bibl, P. Brechlin & E. Rüther

  2. Brigham and Women’s Hospital, Center for Neurologic Diseases, Harvard Medical School, Boston, Massachusetts, USA

    B. Mollenhauer

  3. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany

    H. Esselmann, P. Lewczuk, J. Kornhuber & J. Wiltfang

  4. University of Goettingen, Paracelsus-Elena Klinik, Kassel, Germany

    C. Trenkwalder

  5. Department of Neurology, University of Ulm, Germany

    M. Otto

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  1. M. Bibl
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  2. B. Mollenhauer
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  3. H. Esselmann
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  4. P. Lewczuk
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  5. C. Trenkwalder
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  6. P. Brechlin
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  7. E. Rüther
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  8. J. Kornhuber
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  9. M. Otto
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  10. J. Wiltfang
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Bibl, M., Mollenhauer, B., Esselmann, H. et al. CSF diagnosis of Alzheimer’s disease and dementia with Lewy bodies. J Neural Transm 113, 1771–1778 (2006). https://doi.org/10.1007/s00702-006-0537-z

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  • DOI: https://doi.org/10.1007/s00702-006-0537-z

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