WWOX and early-onset autosomal dominant Alzheimer disease: Unlike the wild-type protein, TPC6AΔ readily undergoes aggregation in the extracellular matrix.1 TPC6AΔ aggregates or plaques have been found in the brain cortex and hippocampus in nondemented middle-aged humans and in patients with Alzheimer’s disease (AD), suggesting that TPC6AΔ is a marker for early onset of AD.1 Also, in 3-week-old Wwox gene knockout mice,1 aggregates of TPC6AΔ, TIAF1 (TGF-β-induced antiapoptotic factor),6,7 tau and amyloid beta (Aβ) can be found in the brain cortex.