title: Strength and weaknesses of cerebrospinal fluid biomarkers in Alzheimer's disease and possible detection of overlaps with frailty process.
abstract: With the increase of human lifespan and refinement of diagnostic techniques dementia, and Alzheimer's disease (AD) in particular, have become a multi-decade process with a complex pathogenesis. The prognosis of AD patients, especially in late stages, may be strongly influenced by factors that go far beyond the well-recognized cascades (tau deposition, amyloid plaques). In this context, AD and Frailty, a multidimensional process of the elderly, inevitably overlap. Not surprisingly, the routine biomarkers collectable in the cerebrospinal fluid, while highly relevant in allowing specific diagnoses, becoming limiting when used to define severity and rate of progression of cognitive impairment. In reviewing merits and pitfalls of routine cerebrospinal fluid profile for AD, this manuscript will examine the state-of-the-art related to a parallel field, the extrapyramidal disorders. For synucleinopathies, we will discuss the possibility to detect factors directly involved in earliest disease pathology (alpha-synuclein, tau-proteins) together with indexes of disease progression (i.e. dopamine-metabolite ratio and loss of blood-brain barrier integrity). This approach might guarantee the capability of monitoring putative disease-modifying strategies. However, we will show the likelihood that nonconventional approaches already proposed for Frail subjects (such as exercise-mediated neuro-protection) might prove to be a useful aid for an ageing brain already impaired by AD alterations. A crucial test for these hypotheses would be to apply this sort of interventional, and not merely pharmacological, therapy to homogeneous patient cohorts.
authors.affiliation: Department of Neuroscience, UOSD Parkinson, University of Rome Tor Vergata, Viale Oxford 81, Rome, Italy. stefani@uniroma2.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
authors.forename: Enrica
authors.initials: E
authors.lastname: Olivola
authors.forename: Mario
authors.initials: M
authors.lastname: Stampanoni Bassi
authors.forename: Valerio
authors.initials: V
authors.lastname: Pisani
authors.forename: Paola
authors.initials: P
authors.lastname: Imbriani
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pierantozzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000209:etiology; D016330:Frail Elderly; D006801:Humans
chemical_list: D015415:Biomarkers