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Resumen Objetivos La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa. La EA es la principal causa de demencia en el mundo, siendo el envejecimiento el principal factor de riesgo. Los criterios diagnósticos para la enfermedad de Alzheimer suelen basarse en datos clínicos. No obstante, es necesario establecer una definición biológica de la enfermedad de Alzheimer basada en biomarcadores que reflejen la neuropatología subyacente. Contenido El objetivo de esta revisión es presentar los resultados obtenidos en la medición de biomarcadores nuevos y ya conocidos en los fluidos biológicos o en neuroimágenes. Resumen Actualmente se emplean tres biomarcadores para el diagnóstico de la enfermedad de Alzheimer_Aβ42, t-Tau y p-Tau. El uso diagnóstico de biomarcadores en el líquido cefalorraquídeo (LCR) presenta algunas limitaciones debido a que la obtención invasiva mediante punción lumbar puede provocar efectos secundarios. La práctica más común en los centros clínicos es la medición en plasma o suero, ya que es mínimamente invasiva y, en consecuencia, se puede obtener y procesar con mayor facilidad. Las dos principales proteínas implicadas en el proceso patológico, Aβ y Tau, se pueden visualizar empleando técnicas de neuroimagen como la PET. Perspectivas Dado que está ampliamente aceptado que la enfermedad de Alzheimer comienza décadas antes de que se diagnostiquen los primeros síntomas clínicos, la detección de alteraciones biológicas previa a la aparición de la sintomatología clínica permitiría su diagnóstico precoz o incluso abriría la puerta a nuevas opciones terapéuticas.

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease. AD is the main cause of dementia worldwide and aging is the main risk factor for developing the illness. AD classical diagnostic criteria rely on clinical data. However, the development of a biological definition of AD using biomarkers that reflect the underling neuropathology is needed. Content The aim of this review is to describe the main outcomes when measuring classical and novel biomarkers in biological fluids or neuroimaging. Summary Nowadays, there are three classical biomarkers for the diagnosis of AD: Aβ42, t-Tau and p-Tau. The diagnostic use of cerebrospinal fluid biomarkers is limited due to invasive collection by lumbar puncture with potential side effects. Plasma/serum measurements are the gold standard in clinics, because they are minimally invasive and, in consequence, easily collected and processed. The two main proteins implicated in the pathological process, Aβ and Tau, can be visualized using neuroimaging techniques, such as positron emission tomography. Outlook As it is currently accepted that AD starts decades before clinical symptoms could be diagnosed, the opportunity to detect biological alterations prior to clinical symptoms would allow early diagnosis or even perhaps change treatment possibilities.

The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27Kip1. At the nuclear level, p27Kip1 has the ability to control the evolution of different phases of the cell cycle and oppose cell cycle progression by binding to CDKs. In the cytoplasm, diverse functions have been described for p27Kip1, including microtubule remodeling, axonal transport and phagocytosis. In Alzheimer’s disease (AD), alterations to cycle events and a purported increase in neurogenesis have been described in the early disease process before significant pathological changes could be detected. However, most neurons cannot progress to complete their cell division and undergo apoptotic cell death. Increased levels of both the p27Kip1 levels and phosphorylation status have been described in AD. Increased levels of Aβ42, tau hyperphosphorylation or even altered insulin signals could lead to alterations in p27Kip1 post-transcriptional modifications, causing a disbalance between the levels and functions of p27Kip1 in the cytoplasm and nucleus, thus inducing an aberrant cell cycle re-entry and alteration of extra cell cycle functions. Further studies are needed to completely understand the role of p27Kip1 in AD and the therapeutic opportunities associated with the modulation of this target.