Neuropathology and biochemistry of early onset familial Alzheimer's disease caused by presenilin-1 missense mutation Thr116Asn.

The majority (~ 55%) of early onset familial Alzheimer disease (FAD) is caused by mutations in the presenilin 1 gene (PSEN1). Here, we describe a family with early onset FAD with a missense mutation in the PSEN1 gene (Thr116Asn). Five family members developed dementia in the third decade of life. One subject underwent autopsy. The onset of clinical symptoms was at the age of 37 years and the disease progressed rapidly. The clinical picture was characterised by progressive memory impairment, amnestic aphasia, and gait disturbances. Neuropathological assessment revealed widespread ß-amyloid (Thal phase 5) and tau (Braak stage 6) pathology. Abundant deposition of diffuse and cored plaques was distributed in cortical and subcortical areas, as well as in the cerebellum, while cotton wool plaques were observed mainly in the occipital cortex. Cerebral amyloid angiopathy was present throughout the brain. In the neocortex, tau pathology, especially neuropil threads, was more abundant in the frontal and occipital cortex and in the hippocampus. Proteomic analyses revealed that the pattern of sarkosyl-insoluble tau was similar to the one seen in sporadic AD. No α-synuclein or TDP-43 pathology was found either in cortical nor in subcortical areas. Here, we present the first comprehensive neuropathological and biochemical study of early onset FAD with a missense mutation Thr116Asn in the presenilin 1 gene. In contrast to other PS1-linked AD patients, the present subject developed cotton wool plaques which were not associated with spastic paraparesis.

Slovak version of the Trail Making Test: Normative data.

The Trail Making Test (TMT) is a popular measure of cognitive functioning, especially processing speed and cognitive flexibility. This study aims to provide normative data for the Slovak adult population. The secondary aim is to test the convergent validity by examining relationships of direct and derived indices to other neuropsychological measures. A sample of 487 healthy adults undertook neuropsychological testing. The relationships of TMT scores to demographic variables and other neuropsychological measures were tested. Age was positively correlated with TMT-A (r = 0.444, p < .01), TMT-B (r = 0.426, p < .01), and the B-A index (r = 0.317, p < .01). Years of education were negatively correlated with TMT-B (r = -0.183, p < .01), B-A difference (r = -0.188, p < .01) and B/A ratio (r = -0.119, p < .01). There were no statistically significant differences in performance based on gender. The test scores were correlated with other measures of processing speed and executive functions. Presented normative data are stratified into 7 age categories. For more accurate interpretation, regression equations were calculated to take years of education into account. TMT-A and B performance, as well as B-A difference score, must be interpreted in relation to age, while education can provide additional information. The B/A ratio is independent from age but should be also corrected for educational level.