Overview

The investigators will compare PI-2620 tau PET scans from patients with frontotemporal lobar degeneration (FTLD), patients with non-amnestic presentations of Alzheimer's disease (naAD), and demographically matched cognitively normal seniors.

Eligibility

Inclusion Criteria: participants must fulfill all of the criteria for one of the following

groups.

Group 1: cognitively and neurologically normal seniors (CN, n=12)

1. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)
2. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
3. Cognitively and neurologically normal according to one of the following criteria:
4. Mini-Mental Status Exam (MMSE; Folstein et al., 1975) score > 27, OR ii. Montreal Cognitive Assessment (MoCA; Carson et al., 2017; Nasreddine et al., 2005) score > 25, OR iii. Global Clinical Dementia Rating of 0, OR iv. Evaluation by a trained clinician
5. Not clinically depressed, according to one of the following criteria:
6. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
7. No history of early-onset neurodegenerative disease in biological siblings or parents, based on the investigators' assessment of the participant's self-reported history.

Group 2: non-amnestic Alzheimer's disease (naAD, n=15)

1. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)
2. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
3. Clinically diagnosed by a trained clinician as having logopenic-variant primary progressive aphasia (lvPPA) or posterior cortical atrophy (PCA).
4. Not clinically depressed, according to one of the following criteria:
5. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
6. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.
7. Group 3: FTLD due to tau (FTLD-tau, n=12)
8. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)
9. If female, post-menopausal or surgically sterile. (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
10. Clinically diagnosed by a trained clinician as having progressive supranuclear palsy (PSP), non-fluent agrammatic primary progressive aphasia (naPPA), or behavioral-variant frontotemporal dementia (bvFTD) consistent with Pick's disease.
11. Not clinically depressed, according to one of the following criteria:
12. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
13. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.
14. Group 4: FTLD due to TDP-43 (FTLD-TDP, n=12)
15. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)
16. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
17. Clinically diagnosed by a trained clinician as having amyotropic lateral sclerosis with frontotemporal dementia (ALS-FTD) or semantic-variant primary progressive aphasia (svPPA).
18. Not clinically depressed, according to one of the following criteria:
19. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
20. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.
21. Group 5: FTLD-tau due to a known genetic mutation (genetic FTLD-tau, n=3)
22. Male or female ≥ 45 years of age
23. Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the MAPT gene.
24. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
25. Clinically diagnosed by a trained clinician as having progressive supranuclear palsy (PSP), non-fluent agrammatic primary progressive aphasia (naPPA), or behavioral-variant frontotemporal dementia (bvFTD) consistent with Pick's disease.
26. Not clinically depressed, according to one of the following criteria:
27. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
28. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.
29. Group 6: FTLD-TDP due to a known genetic mutation (genetic FTLD-TDP, n=3)
30. Male or female ≥ 45 years of age
31. Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the GRN gene or in open reading frame 72 of chromosome 9 (C9orf72).
32. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
33. Clinically diagnosed by a trained clinician as having amyotropic lateral sclerosis with frontotemporal dementia (ALS-FTD) or semantic-variant primary progressive aphasia (svPPA)
34. Not clinically depressed, according to one of the following criteria:
35. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician
36. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.
37. Group 7: amnestic Alzheimer's disease (naAD, n=15)
    1. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873) 2. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).
    2. Clinically diagnosed by a trained clinician as having amnestic mild cognitive impairment (MCI) or amnestic Alzheimer's disease (aAD).
    3. Not clinically depressed, according to one of the following criteria: i. Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii. Evaluation by a trained clinician 5. Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

Exclusion Criteria for all groups:

Participants will be excluded from enrollment if they meet any of the following criteria.

1. The participant has any medical or psychiatric conditions that, in the opinion of the investigator, would compromise the participant's safety or successful participation in the study.
2. The investigators of UNICORN (IRB #842873) have determined the participant has evidence of structural abnormalities such as major stroke or mass on MRI that is likely to interfere with analysis of the PET scan.
3. The participant is unable to tolerate or have a contraindication to imaging procedures in the opinion of an investigator.
4. The participant has a history of significant or ongoing alcohol abuse or substance abuse, or dependence based on medical record review or self-reported.
5. The participant is enrolled in a clinical trial for a disease-modifying treatment that targets the molecular pathology underlying their neurodegenerative disease.