A multiancestral genome-wide exome array study of Alzheimer disease, frontotemporal dementia, and progressive supranuclear palsy.

Importance: Previous studies have indicated a heritable component of the etiology of neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few have examined the contribution of low-frequency coding variants on a genome-wide level.

Objective: To identify low-frequency coding variants that affect susceptibility to AD, FTD, and PSP.

Alzheimer's disease neuropathologic changes in semantic dementia.

Unlabelled: Neuropathologic change underlying primary progressive aphasia (PPA) most commonly includes one of the frontotemporal lobar degenerations, such as FTLD-tau or FTLD-ubiquitin. The next most frequent etiology of PPA is Alzheimer's disease (AD). We describe 5 subjects with clinical diagnoses of semantic dementia, who underwent longitudinal clinical evaluation and postmortem neuropathology examination of the central nervous system.

Increased prevalence of significant recurrent headache in preclinical familial Alzheimer's disease mutation carriers.

Background/aims: A previous study found a high prevalence of headaches in persons with familial Alzheimer's disease (FAD) due to a PSEN1 mutation. In our study we compared the prevalence of headaches between nondemented FAD mutation carriers (MCs) and non-mutation-carrying controls (NCs).

Methods: A headache questionnaire that assessed the prevalence of significant headaches and diagnosis of migraine and aura by ICHD-2 criteria was administered to 27 individuals at risk for FAD.

Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations.

Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation.

The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families.

Nine families with autosomal dominant Alzheimer's disease (AD), all of whom had the Ala431Glu substitution in the PSEN1 gene and came from Jalisco State in Mexico, have been previously reported. As they shared highly polymorphic flanking dinucleotide marker alleles, this strongly suggests that this mutation arose from a common founder. In the current letter, we expand this observation by describing an additional 15 independent families with the Ala431Glu substitution in the PSEN1 gene and conclude that this mutation is not an uncommon cause of early-onset autosomal dominant AD in persons of Mexican origin.

Performance on MMSE sub-items and education level in presenilin-1 mutation carriers without dementia.

Background: Spanish-language screening tests that are sensitive to the early cognitive changes of Alzheimer's disease (AD) are needed. Persons known to be at 50% risk for young-onset AD due to presenilin-1 (PSEN1) mutations provide the opportunity to assess which measures on the Mini-mental State Examination (MMSE) are most sensitive to these early changes.

Methods: We performed genetic and Spanish-language cognitive testing on 50 Mexican persons without dementia at risk for inheriting PSEN1 mutations.

Urinary retention in a patient with West Nile virus.

West Nile Virus (WNV) has received much recent attention due to multiple outbreaks in North America, its insidious onset in many patients, and a wide variety of neurologic manifestations. A 45-year-old man who exhibited urinary retention as a presenting symptom of WNV infection is presented herein. We believe this to be the first reported case of a urologic sequela secondary to WNV infection.