Patients
Neurodegenerative Diseases
Tauopathies and alpha-synucleinopathies play a critical role in a range of neurodegenerative diseases. Tau can accumulate in different parts of the brain, leading to several neurodegenerative disorders. Alpha-synucleinopathies are neurodegenerative disorders caused by aggregation of abnormal alpha-synuclein proteins (αSyn) with formations of insoluble fibrils in neurons and glia.
Some examples of these disorders are described below.
The Threat to Human Health
Approximately
people worldwide suffer from AD
An estimated
people will be diagnosed with AD by 2050
Approximately
people are affected by Parkinson’s disease (PD)
Alzheimer’s disease (AD)
AD, the most prevalent form of dementia, is characterized by progressive memory loss and cognitive deficits. Pathology is comprised of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. It is further characterized by the accumulation of 3-repeat (3R) and 4-repeat (4R) forms of tau. Progression of AD, in part, reflects the prionlike spread of Tau aggregates across brain regions, possibly along neuronal networks connected by synapses. Recent studies have shown that tau pathology is closely correlated with cognitive decline in AD patients. Thus, anti-tau immunotherapies have recently become a major emphasis of the potential treatments for AD.
There are also primary tauopathies where either the 3R or 4R forms of tau accumulate in different brain regions, leading to several neurodegenerative disorders.
Frontotemporal dementia (FTD)
FTD is the second leading cause of early-onset dementia. It is characterized by atrophy of the the frontal and temporal lobes resulting from neuronal loss, spongy changes, and gliosis. In 20% to 30% of patients, it is caused by mutations in the genes that code for tau protein or other proteins that play an important role in brain function. Clinically, patients present with behavioral and/or language impairments, but they can also present with motor impairment such as those seen in patients with PD, PSP and CBD. During the early stages, it can be difficult to differentiate among these different types of FTD.
Pick’s disease (PiD)
PiD is a form of FTD characterized by specific lesions named “Pick bodies” that are found in the hippocampus and frontal cortex, resulting in progressive dementia. Pick bodies are mostly formed from the accumulation of abnormal 3R tau proteins. Therefore, more precise diagnostic approaches, such as PET imaging and plasma or cerebrospinal fluid (CSF), are needed to identify biomarkers. There are no approved treatments that change the course of the disease.
Corticobasal degeneration (CBD)
CBD is a rare condition that can cause gradually worsening problems with movement, speech, memory, and swallowing. As with other tauopathies, in the early stages it can be confused with PD, PSP, or LBD. Patients with CBD experience atrophy in frontal brain regions and basal ganglia due to accumulation of the 4R form of tau proteins.
Parkinson’s disease (PD)
PD is the second most common neurodegenerative disorder and results from the loss of neurons in an important brain region called the “substantia nigra,” which regulates dopamine levels in the basal ganglia, a brain region that controls motor function. PD is mainly caused by the accumulation of abnormal forms of alpha-synuclein, a protein believed to play a role in neuronal communication. As a result, the brains of patients with PD show progressive decreases in dopamine levels. Patients with PD typically present with motor impairments, such as slowing of gait, tremor, and loss of balance, but can also show nonmotor symptoms, including psychiatric and sleep disturbances. Although there are many effective treatments available for the motor symptoms of PD, there is no approved treatment that can alter the course of the disease.
Lewy body dementia (LBD)
LBD is another neurodegenerative disorder, which like PD, that results from the accumulation of aggregated forms of alpha-synuclein in the brain called “Lewy bodies.” Patients with LBD typically present with neuropsychiatric symptoms, often visual hallucinations, progressive decline in cognitive function, and later in the course of the disease, motor deficits similar to those seen in PD. As with the other ɑ-synucleinopathies, there are no approved treatments that can slow or stop progression of this condition.
Clinical Trial Information
Identifier Status
APRINOIA Therapeutics Inc.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of APNmAb005 in Healthy Subjects
NCT05344989
APRINOIA Therapeutics Inc.
APN1607-201
Evaluation of [18F]APN-1607 positron emission tomography (PET).
Uptake in AD Patients
Compared With Healthy Subjects
NCT04141150
Suzhou APRINOIA Therapeutics Co., Ltd
APN-1607-301
A Phase 3, Multicenter Study of [18F]APN-1607 PET in Subjects With AD Compared to HC
In progress
Nanjing First Hospital, Nanjing Medical University
Clinical Evaluation of [18F]APN-1607 PET Uptake in Alzheimer’s Disease Patients
NCT05043675
Chang Gung Memorial Hospital, Linkou
Topography Staging and Dual Phase Image Quantification of Tau PET in Cognitive Impairment Subjects
NCT04169126
Chang Gung Memorial Hospital
Image Characteristic and Longitudinal
Follow-up of 18F-PMPBB3 (APN-1607) PET for Progressive Supranuclear Palsy
NCT04541836
National Taiwan University Hospital
Establishing 18F PMPBB3 (APN 1607) PET Imaging Markers for Diagnosis of Tauopathy Parkinsonism Syndromes
NCT04557865
Patient Advocacy
The Alzheimer’s Association
225 N Michigan Ave, 17th floor,
Chicago, IL 60601
800.272.3900
https://www.alz.org/help-support
American Parkinson Disease Association
POB 61420
Staten Island, NY 10306
800.223.2732
https://www.apdaparkinson.org/
Alzheimer’s Foundation of America
322 Eighth Avenue, 16th floor
New York City, NY 10001
866.232.8484
https://alzfdn.org/
Parkinson’s Foundation
200 SE 1st Street, Suite 800,
Miami, FL 33131
800.473.4636
https://www.parkinson.org/
The ALS Association
1300 Wilson Boulevard, Suite 600
Arlington, VA 22209
800.782.4747
https://www.als.org/
Cure Progressive Supranuclear Palsy
1216 Broadway, 2nd floor
New York City, NY 10001
800.457.4777
https://www.psp.org/ineedsupport/supportgroups/
Northeast Amyotrophic Lateral Sclerosis Consortium (NEAL)
177 E Colorado Blvd, Suite 200
Pasadena, CA 91105-1955
855.437.4823
https://www.neals.org/
Lewy Body Dementia Association
912 Killian Hill Road, SW
Liburn, GA 30047
800.539.9767
https://www.lbda.org/lbda_support_group/support-group-for-family-care-partners-for-dementia-with-lewy-body/
Michael J. Fox Parkinson’s Disease Foundation
POB 4777
New York City, NY 10163-4777
212.509.0995
https://www.michaeljfox.org/
National Organization for Rare Disorders (NORD)
1900 Crown Colony Drive, Suite 310
Quincy, MA 02169
617.249.7300
https://rarediseases.org/