This is an open-label study without randomisation. All eligible patients will receive two administrations of the investigational imaging agent [18F]PI-2620 at a radioactive dose of 185 MBq, one with high specific activity (≤ 5 µg tracer mass dose), another one with low specific activity (40-50 µg tracer mass dose).

This is an open-label, single center study to visually assess and quantitatively compare brain PET images obtained after application of [18F]PI-2620 with different specific activities: 1) High specific activity (low mass dose): 185 MBq containing a maximum mass dose of ≤5 μg in up to 10 mL and 2) Low specific activity (high mass dose): 185 MBq containing a maximum mass dose of 40-50 μg in up to 10 mL).

Inclusion Criteria:

• Males and females aged 50-80 years
• Able to understand, sign and date written informed consent, which is confirmed by the judgment of the referring physician
• Written informed consent must be obtained before any assessment is performed
• Prior evaluable MRI
• Female patients must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause). If they are of child-bearing potential, must commit to use of a highly effective contraceptive measure for the duration of the study
• Male patients and their partners of childbearing potential must commit to the use of a highly effective method of contraception for a minimum of one week following each PET scan
• Male patients must commit to not donate sperm for a minimum of one week after each PET scan.

Inclusion Criteria for mild-moderate AD patients

• Patients with mild or moderate AD in accordance with NIA-AA guidelines 2011
• Have a CDR score of ≥ 0.5 at screening
• Have an MMSE score of ≤ 24 at screening
• Prior evaluable amyloid PET imaging confirming presence of beta-amyloid brain pathology
• Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before the [18F]PI-2620 PET imaging visits

Inclusion Criteria for patients with probable PSP

• Patients with a clinical diagnosis of probable PSP based on the Movement Disorder Society criteria (Höglinger et al., 2017).
• Have a PSP rating score between 20 - 60
• Medications taken for symptomatic treatment of PSP must be maintained on a stable dosage regimen for at least 30 days before the [18F]PI-2620 PET imaging visits

Exclusion Criteria (for all patients)

• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness equivalent to CTC v5.0 (common toxicity criteria) toxicities greater than grade 2
• Evidence of clinically significant disease that is expected to interfere with cognitive assessments or the ability to complete the study procedures
• Patient has received an investigational drug including treatments targeting amyloid-beta plaques or tau within 3 months of screening
• Pregnant (or intention of getting pregnant), lactating or breastfeeding
• MRI exclusion criteria include: Findings of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct >1 cm3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the Fluid-Attenuated Inversion Recovery (FLAIR) sequence that is >=20 mm in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with Central Nervous System (CNS) disease
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI
• Unwilling and/or unable to cooperate with study procedures