Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer’s disease and mild cognitive impairment

Abstract

To cite this version:Lars Olson, Christian Humpel. Growth factors and cytokines/chemokines as surrogate biomarkers in cerebrospinal fluid and blood for diagnosing Alzheimer´s disease and mild cognitive impairment. Experimental Gerontology, Elsevier, 2009, 45 (1) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT 3The life expectancy of humans has markedly increased within the last 100 years. As age is the main risk factor for Alzheimer´s disease (AD), the number of patients suffering from AD, and mixed forms of dementia will increase within the next 50 years. It is expected that there will be about 80 million AD patients worldwide in 2050.The establishment of reliable diagnostic surrogate markers for AD and measures to monitor disease progression is essential in order to evaluate novel treatmens to counteract and/or delay symptoms in AD and to allow initiation of therapeutic interventions as early as possible. A valid and easily accessible diagnostic procedure should be the basis for the treatment. The search for biomarkers becomes extremely important, due the large expected increase in dementia and AD patients within the next 50 years. It will be necessary to find "biomarkers of aging" and "biomarkers of disease". While a "biomarker of aging" may allow to follow up individuals over several years, a "biomarker of disease" will directly reflect the stage of the disease process (for details on diagnosis see Sprott as well as Cedazo-Minguez and Bengt Winblad; both this special issue of EXG). Briefly, we need to distinguish between biomarkers (1) that add to diagnostic certainty in the setting of a clinical evaluation, (2) those that can be used in lieu of a clinical evaluation, and (3) those that can be used to track disease progression at a specific stage. Although the Diagnosis of Alzheimer´s disease and other forms of dementia ACCEPTED MANUSCRIPT4 same biomarker could in theory be used in all these settings, most do not perform evenly across them. In addition, some biomarkers are more reasonably thought about as "risk factors" rather than "true disease" markers. In order for a diagnostic biomarker to be useful, certain criteria need to be met ).(1) The biomarker should reflect some basic pathophysiological processes, and detect a fundamental feature of the disease with high sensitivity and specificity.(2) The biomarker should be specific for the disease compared with related disorders. give an overview on the measurement of growth factors and cytokines/chemokines in CSF and blood. It will be shown, that all mentioned factors show a very high heterogenity between the...

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“…Previous studies show conflicting results for inflammatory markers in AD (Olson and Humpel 2010). Adding to this, we could not replicate previous findings of increased CCL2 in AD, despite using an ELISA from the same manufacturer as one of the previous studies (Blasko et al 2006) and two independent assays.…”

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…However conflicting results exist about the pertinence of the use of these peripheral biomarkers. Among the inflammatory markers several cytokines have been measured in CSF or blood, such as interleukin 1- and 1-, interleukin-6, -10, -11 and -18, and tumor necrosis factor-alpha (for review see Casoli et al, 2010;Olson & Humpel, 2010). But the results are very divergent between the different groups.…”

Chemokines in CSF of Alzheimer's disease patients

“…AD is morphologically characterized by extracellular beta-amyloid (BA) plaque deposition, intraneuronal tau-pathology, neuronal cell death, vascular dysfunction and inflammatory processes [1][2][3] . Cerebrospinal fluid (CSF) closely reflects the composition of the brain extracellular space and is likely to have the highest yield of biomarkers for the evaluation of dementia 4 .…”

“…The dementing diseases represent a growing medical, economic and social problem and Alzheimer's disease (AD) is the most common cause of dementia associated with advancing age 1 . AD is morphologically characterized by extracellular beta-amyloid (BA) plaque deposition, intraneuronal tau-pathology, neuronal cell death, vascular dysfunction and inflammatory processes [1][2][3] .…”