A neuronal protein involved in synaptic function that, when misfolded and aggregated, contributes to neurodegenerative diseases such as Parkinson’s disease and related synucleinopathies.

A biologically active compound produced when a drug is metabolized, contributing to the drug’s therapeutic or adverse effects.

Any unintended or harmful medical occurrences in a clinical trial participant who is receiving a drug or undergoing a study procedure, which does not necessarily have a causal relationship with the treatment.

Parkinsonian trait characterized by reduced movement initiation (akinesia) and increased muscle tone (rigidity), usually with little or no tremor.

In the context of PSP, it refers to an acquired, progressive impairment of language function that can manifest as non-fluent, agrammatic speech, effortful and halting verbal output, and deficits in syntactic comprehension.

Impairment of the ability to perform purposeful, skilled movements that cannot be explained by basic motor deficits such as weakness, rigidity, bradykinesia, or tremor. In PSP, apraxia is most commonly ideomotor apraxia, which manifests as difficulty in executing learned movements on command or by imitation, despite intact comprehension and basic motor function, but other types as limb-kinetic apraxia (clumsy, imprecise movements, and difficulty with fine motor tasks) or apraxia of speech (effortful, halting speech with sound distortions) could also occur in specific phenotypes or advanced disease.

A measure of the total drug exposure over time, representing the area under the plasma concentration-time curve.

Reactive proliferation and hypertrophy of astrocytes in response to neural injury or disease, contributing to inflammation and scar formation in the central nervous system.

Shrinkage of tissue visible on imaging tests. In the case of the PSP, it refers to loss of brain volume.

A pattern of inheritance where only one copy of a mutated gene is enough to cause the disease.

The bidirectional movement of cellular structures, proteins, and other materials within neurons, essential for maintaining neuronal function and survival.

A measurable (quantifiable) biological indicator (in blood, spinal fluid, or brain imaging) used for diagnosis, prognosis, and as an endpoint in clinical trials.

A biological barrier created by closely connected cells that regulate the passage of molecules from the blood into the central nervous system. It selectively permits essential substances such as water, oxygen, and certain drugs to enter the brain while restricting others.

Slowness of movement, which can also encompass a difficulty initiating movement.

Noticeable slowing of thought processes, evident to the patient or to someone familiar with them.

Neurological control of muscles involved in speech, swallowing, and chewing.

A type of observational study that compares two groups of people (those with the disease or condition under study (cases) and people who do not have the disease or condition (controls)) and retrospectively examines their prior exposure to a particular factor of interest.

Impaired coordination of voluntary movements (ataxia) due to cerebellar dysfunction.

The fluid that surrounds and fills the brain and spinal cord, protecting the brain, providing nourishment for cells, and removing waste.

A research study conducted in humans to evaluate the safety, efficacy, and optimal use of medical interventions such as drugs, devices, or therapies.

The maximum (peak) concentration of a drug found in blood or plasma after the administration.

The presence of multiple pathologies occurring at the same time in the same person. In PSP, co-pathologies are common and may include additional neurodegenerative changes, such as Alzheimer’s disease-related amyloid plaques, Lewy body pathology and age-related cerebrovascular changes, which may contribute to clinical variability and complicate diagnosis.

The co-occurrence of multiple disorders in the same individual, which can influence the diagnosis, treatment, or prognosis of some conditions.

Neurodegenerative syndrome combining movement disorder signs (rigidity, apraxia, dystonia, myoclonus) with cortical signs (apraxia, sensory loss, alien limb).

Descriptive analyses that estimate the overall costs associated with a disease. These studies quantify the economic burden by measuring direct, indirect, and sometimes intangible costs, but they do not compare alternative interventions or relate costs to health outcomes. Instead, they provide baseline data on disease burden, which can inform subsequent economic evaluations and policy decisions.

A loss of global cognitive ability that interferes with normal social or occupational function.

The process of distinguishing a disease from other conditions with similar clinical features. In PSP, it involves differentiating it from disorders such as Parkinson’s disease or other PSP-mimicking syndromes.

Is a generic measure of health outcome that can be used in cost utility analysis. DALYs are a measure of overall disease burden, expressed as the number of years lost due to ill health, disability or mortality. 

The overall impact of a disease on patients, caregivers, and healthcare systems – including physical, emotional, social, and economic effects.

A treatment aimed at addressing the underlying cause and altering its natural progression. These work by targeting the root mechanisms that drive the disease, potentially slowing down, halting or even reversing its course.

A study design where neither participants nor researchers know which treatment each participant receives, reducing the likelihood of bias in the results.

A speech disorder of neurological origin marked by impaired articulation.

An alteration or distortion in the normal sense of taste.

Difficulty swallowing that often requires changes in diet. Some individuals with dysphagia struggle with certain foods or liquids, while others are unable to swallow at all. Additional signs may include coughing or choking during meals, regurgitating food, feeling as though food is stuck in the throat or chest, and continuous drooling.

In the medical context refers to the total financial impact that a disease or health condition imposes on individuals, households, healthcare systems, and society. This burden is typically divided into direct costs (such as expenditures for medical care, hospitalizations, medications, diagnostic tests, and preventive actions) and indirect costs (including lost productivity, absenteeism, presenteeism, loss of income, and premature death).

The ability of an intervention to produce the intended effect under controlled study conditions.

A predefined variable or outcome used to evaluate the effect, safety, or other impact of a treatment or intervention. For example, the primary efficacy endpoint in PROSPER is the change from baseline to Week 52 on the PSP Rating Scale (PSPRS).

Refers to heritable changes that do not affect the DNA sequence but influence gene expression (e.g., chemical modifications).

Located or occurring outside the cell.

Inability to voluntarily open the eyelids after they have been closed for a period of time.

Cases of PSP that occur in multiple members of the same family, suggesting a hereditary component.

Investigational, brain-penetrant, selective OGA inhibitor intended as a potential DMT for PSP.

Defined as at least three of the following features, which have to be persistent: apathy; bradyphenia; dysexecutive syndrome; reduced phonemic verbal fluency; impulsivity, disinhibition, or perseveration.

Impairment of the frontal lobe, which affects executive, cognitive, or behavioral functions.

Sudden and transient inability to initiate walking, often described as the feet being “glued” to the floor.

A segment of genetic material (or DNA) that determines inherited characteristics and contributes to the organism’s physiological functions.

The specific physical location of a gene or other DNA sequence on a chromosome.

A research method that examines the entire genome (the complete set of DNA of a person) to detect genetic variants linked to a specific trait or disease.

A protein expressed almost exclusively in astrocytes, used as a biomarker of astrocyte injury and neuroinflammation.

Refers to the quantifiable use of healthcare services and resources, including hospitalizations, outpatient visits, emergency department visits, medication prescriptions, use of medical devices, allied health services, and home care. HCRU is a key metric in health services research and health economics, used to assess disease burden, plan resource allocation, and evaluate the impact of interventions on healthcare systems.