Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia

Primary progressive aphasia (PPA) is an umbrella term that encompasses a group of
neurodegenerative syndromes characterized by varying combinations of progressive speech and
language problems. Three clinical variants of PPA have been described and are well
recognized: the agrammatic variant characterized by grammatical errors in speech and writing
and typically associated with phonetic errors in speech; the semantic variant characterized
by poor naming from loss of knowledge about the meaning of words; and the logopenic variant
characterized by word retrieval problems and poor sentence repetition from impairment of
working memory and phonemic errors. Pathological studies of PPA patients that died with
postmortem examination of their brains have demonstrated that PPA is associated with a number
of different abnormal cellular proteins that do not have perfect associations with the three
PPA variants. One such protein is the microtubule associated protein, tau, which is the most
common abnormal protein found in the brains of patients with PPA. Tau is an important protein
that has been linked to the neurodegenerative process in many diseases. No neuroimaging
studies have investigated tau deposition in PPA and hence the binding characteristics of
AV-1451 (the Tau binding drug used in this study) in PPA are unknown. Understanding the
binding characteristics of AV-1451 is crucial to help determine whether it can serve as a
biomarker for tau deposition in the brains of patients with PPA.

Inclusion Criteria:

- Must be over the age of 18

- Must speak English as your primary language

- Must have an informant who can provide independent evaluation of functioning

- Must present with a chief complaint of progressive impairment of speech or language

- Must fulfill diagnostic criteria for Primary Progressive Aphasia

Exclusion Criteria:

- Any subject who is mute or whose speech is unintelligible will be excluded

- All subjects with concurrent illnesses that could account for speech and language
deficits, such as traumatic brain injury, strokes or developmental syndromes, and
subjects meeting criteria for another neurodegenerative disease, such as amnestic
Alzheimer's type dementia, dementia with Lewy bodies, behavioral variant
frontotemporal dementia, progressive supranuclear palsy, and corticobasal syndrome
will be excluded

- Subjects who meet criteria for PPA and have mild behavioral changes, eye movement
abnormalities or mild limb apraxia but who do not meet diagnostic criteria for
behavioral variant frontotemporal dementia, progressive supranuclear palsy, or
corticobasal syndrome respectively, will also be excluded

- All pregnant, post-partum and breast-feeding women will be excluded

- Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace
maker, etc.), if there is severe claustrophobia, if there are conditions that may
confound brain imaging studies (e.g. structural abnormalities, including subdural
hematoma or intracranial neoplasm), or if they are medically unstable or are on
medications that might affect brain structure or metabolism,(e.g. chemotherapy).