An Autopsy Proven Child Onset Chronic Traumatic Encephalopathy

Here we present an autopsy case of chronic traumatic encephalopathy (CTE) in a 36-year-old man. He had a history of febrile seizures at the age of four and was severely demented at age 10 when he was admitted to a mental hospital. He had suffered repetitive self-harm, such as frequent banging of the head on the wall in his hospital record, but he had no clear history between the ages of four and ten. Autopsy revealed global cerebral atrophy, including the basal ganglia, thalamus, hippocampus, amygdala, mammilary bodies and lateral geniculate bodies. This case showed typical pathological features of CTE. Phosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs) and neuropil threads (NT) we are widely distributed in the brain, especially in the depth of the cerebral sulci. NFT and NT were also found in the basal ganglia, thalamus, amygdala and brainstem. Scanty β-amyloid deposits were found in the motor and sensory cortices, but α-synuclein was completely negative in the brain. This example showed that CTE can occur in young ages and that even children can experience CTE dementia.

The Interface between Cytoskeletal Aberrations and Mitochondrial Dysfunction in Alzheimer's Disease and Related Disorders

The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Abeta in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Abeta oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Abeta to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Abeta oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Abeta generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and beta-integrins are physically associated with each other.