Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

The purpose of this study is to test the effects of long-term therapeutic doses of
formoterol, on a) cerebrospinal fluid CSF tau levels, and A-beta amyloid protein 40/42
levels, and b) cognitive function: NE-ergic neurons undergo significant degeneration in AD.
This system plays a significant role in cognition. Recent studies have indicated that
increasing NE levels in the brain would significantly improve microglia migration and
clearance of A-beta amyloid protein 40/42 levels in mouse models of AD. The investigators
plan to test whether long- term daily treatment with inhaled formoterol solution would
improve the structure and function of hippocampal neurons in AD. Study Design: Randomization
and initiation of experimental treatment: All participants will be given formoterol daily for
52 weeks. The active regimen will be initiated as (20 micro gram, BID). The dose will be
decreased if there is evidence of side effects, including cardiac or respiratory alteration
changes, gastro-intestinal disturbances or neurological issues.

Inclusion Criteria:

- Males and females between the ages of 50-85,

- Mild-to-moderate AD (NINCDS/ADRDA criteria for probable AD will be used to establish
AD diagnosis).

- MMSE 16-26.

Exclusion Criteria:

- Non-AD dementia or significant neurological disease such as Parkinson's disease,
stroke, brain tumor,multiple sclerosis, seizure disorder, focal brain lesion, or head
injury with loss of consciousness.

- Hypothyroidism, congestive heart failure (New York Heart Association Class III or IV),
significant extrapyramidal symptoms on neurological examination, serum creatinine>1.3
mg/dl, significant arrhythmias or conduction defect abnormalities on ECG,

- Use of another beta2 adrenergic drug within the last 2 months.

- Residence in a long-term care facility.

- Evidence of any significant clinical disorder or laboratory finding that renders the
person unsuitable for receiving an investigational new drug.

- Known hypersensitivity or prior exposure to formoterol.

- Active asthma or family history of asthma.