Tauopathies with parkinsonism: Clinical spectrum, neuropathologic basis, biological markers, and treatment options

Department of Neurology, University of Ulm, Ulm, Germany.
European Journal of Neurology (Impact Factor: 4.06). 04/2009; 16(3):297-309. DOI: 10.1111/j.1468-1331.2008.02513.x
Source: PubMed


Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.

Download full-text


Available from: Zygmunt Jamrozik,
  • Source
    • "Progressive supranuclear palsy (PSP) is characterized by Parkinsonism associated with signs like supranuclear gaze palsy, early falls, dysphagia, dysarthria, axially pronounced rigidity, and behavioral/cognitive impairment [71]. PSP can be subdivided into different subtypes that are characterized by their clinical course, most probably related to different patterns of pathological tau distribution in the brain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The evolution of the fovea centralis, the most central part of the retina and the area of the highest visual accuracy, requires humans to shift their gaze rapidly (saccades) to bring some object of interest within the visual field onto the fovea. In addition, humans are equipped with the ability to rotate the eye ball continuously in a highly predicting manner (smooth pursuit) to hold a moving target steadily upon the retina. The functional deficits in neurodegenerative movement disorders (e.g., Parkinsonian syndromes) involve the basal ganglia that are critical in all aspects of movement control. Moreover, neocortical structures, the cerebellum, and the midbrain may become affected by the pathological process. A broad spectrum of eye movement alterations may result, comprising smooth pursuit disturbance (e.g., interrupting saccades), saccadic dysfunction (e.g., hypometric saccades), and abnormal attempted fixation (e.g., pathological nystagmus and square wave jerks). On clinical grounds, videooculography is a sensitive noninvasive in vivo technique to classify oculomotion function alterations. Eye movements are a valuable window into the integrity of central nervous system structures and their changes in defined neurodegenerative conditions, that is, the oculomotor nuclei in the brainstem together with their directly activating supranuclear centers and the basal ganglia as well as cortical areas of higher cognitive control of attention.
    Journal of Ophthalmology 05/2014; 2014(2):658243. DOI:10.1155/2014/658243 · 1.43 Impact Factor
  • Source
    • "Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease that causes the gradual deterioration and death of specific volumes of the brain (Richardson et al., 1963; Steele et al., 1964). Ludolph and colleagues showed that the neuropathologic features of PSP include marked midbrain atrophy and atrophy of the pallidum, thalamus, subthalamic nucleus, and frontal lobes (Ludolph et al., 2009). Clinical criteria for the diagnosis of PSP are: a gradually progressive disorder, an onset at the age of 40 years or later, a presence of vertical supranuclear palsy, a slowing of vertical saccades and a postural instability with falls in the first year of disease onset. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and Purpose: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. Over the last years the introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. This observational trial is aimed at investigating the changes in the main spatiotemporal following end-effector robot training in people with PSP. Method: Pilot observational trial. Participants: Five cognitively intact participants with PSP and gait disorders. Interventions: Patients were submitted to a rehabilitative program of robot-assisted walking sessions for 45 min, 5 times a week for 4 weeks. Main outcome measures: The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded by a gait analysis laboratory. Results: Robot training was feasible, acceptable and safe and all participants completed the prescribed training sessions. All patients showed an improvement in the gait spatiotemporal index (Mean velocity, Cadence, Step length, and Step width) (T0 vs. T1). Conclusions: Robot training is a feasible and safe form of rehabilitation for cognitively intact people with PSP. The lack of side effects and the positive results in the gait parameter index in all patients support the recommendation to extend the trials of this treatment. Further investigation regarding the effectiveness of robot training in time is necessary. Trial registration: ClinicalTrials.gov NCT01668407.
    Frontiers in Human Neuroscience 04/2014; 8(1):207. DOI:10.3389/fnhum.2014.00207 · 3.63 Impact Factor
  • Source
    • "Its etiology is unknown. From a pathological point of view, the disease consists in a neurodegenerative process that involves the basal ganglia, the brainstem, the prefrontal cortex and the cerebellum, with accumulation of a tau protein - hence the classification as tauopathy [3]. Onset typically occurs after 40 years of age. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of taupathies and involves both cortical and subcortical structures. No effective therapy is to date available.Methods/design: Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors.Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this "first-in-man" approach and to preliminarily explore its efficacy by excluding the placebo effect.Trial registration: NCT01824121.
    Journal of Translational Medicine 01/2014; 12(1):14. DOI:10.1186/1479-5876-12-14 · 3.93 Impact Factor
Show more