1. 1. To determine the spatial localization of FlnA in post-mortem AD brain.
2. 2. To determine the relationship between FlnA and amyloid precursor protein (APP).

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and a leading cause of dementia in the elderly population. It presents with increasing impact on public health, including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. Thus, developing a sensitive and predictive biomarker that detects disease onset is imperative.

Prior studies have implicated a role for the actin binding protein filamin A (FLNA) in the pathogenesis of AD. FLNA regulates the acetylcholine receptor, Wnt cascade, presenilin function and tau pathology. Each of these molecular pathways has been implicated in AD pathogenesis, but the manner by which FLNA might regulate these processes in the central nervous system remains unclear. Hence, our overarching goal is to determine the potential role of FLNA in AD pathogenesis.

1. 1. Immunohistochemical staining of FlnA, cell-specific, and beta amyloid markers was performed on brain tissue of healthy controls and AD patients.
2. 2. Transient FLNA and APP overexpression in a melanoma cell line.
3. 3. Co-immunostaining of FLNA and APP with protein trafficking markers in a human astrocytoma cell line.

1. 1. FLNA is predominantly expressed within brain reactive astrocytes and increased numbers of FLNA-positive astrocytes are seen with worsening AD severity.
2. 2. FLNA regulates APP expression and conversely, APP regulates FLNA expression.
3. 3. FLNA co-localizes with APP in the endosomes and to a lesser degree, in lysosomes.

These observations suggest that FLNA is involved in the trafficking of AD associated proteins in astrocytes, thereby regulating their signaling pathways and AD progression. A better understanding of this relationship may ultimately lead to strategies to modulate trafficking protein activity for development of biomarkers and therapeutic interventions.