In Alzheimer's disease (AD) brain, exposure of axons to Aβ causes pathogenic changes that spread retrogradely by unknown mechanisms, affecting the entire neuron. We found that locally applied Aβ1-42 initiates axonal synthesis of a defined set of proteins including the transcription factor ATF4. Inhibition of local translation and retrograde transport or knockdown of axonal Atf4 mRNA abolished A...

This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was ...

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected ...

Soluble oligomers of amyloid-β (Aβ) peptides (AβOs) contribute to neurotoxicity in Alzheimer's disease (AD). However, it currently remains unknown whether an increase in AβOs is the common phenotype in cellular and animal models. Furthermore, it has not yet been established whether experimental studies conducted using models overexpressing mutant genes of the amyloid precursor protein (APP) are...

The accumulation of amyloid-β protein (Aβ) is significant in the pathogenesis of Alzheimer's disease. Several previous studies indicate that the NR2B‑containing N‑methyl‑D‑aspartate receptors are critically involved in the Aβ mediated disruption of neuronal function. Diazoxide (DZ), a highly selective drug capable of opening mitochondrial ATP‑sensitive potassium channels, has neuroprotective ef...

The captions for Figure 2C,D have several minor errors numbering of the residues of Aβ. The corrected captions should read: (C) NMR-based structural model of Aβ1−40 fibrils showing central residues K16−D22 and A30−V36. (D) NMR-based structural model of Aβ1−42 fibrils showing central residues L17−I41. These errors are peripheral to this paper and do not affect the results or conclusions in any way.

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective o...

BACKGROUND Cerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD). OBJECTIVE We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS We measured CSF amyloid-β (Aβ) 1-42, total tau (t-tau), and phosphorylated t...

OBJECTIVES The purpose of this study was to carry out systematic review of the literature and meta-analysis to evaluate the diagnostic utility of cerebrospinal fluid (CSF) levels of the 42 amino acid form of amyloid-beta (Aβ1-42) as a biomarker for differentiating Alzheimer's disease (AD) from non-AD dementia. METHODS Design. Systematic literature review was used to evaluate the effectiveness...