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October 28, 2014
Alzheimer's & Dementia: The Journal of the Alzheimer's Association September 2014
Biological heterogeneity in ADNI
amnestic mild cognitive impairment
Previous work examining normal controls from the Alzheimer's
Disease Neuroimaging Initiative (ADNI) identified substantial biological
heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI)
subjects would also exhibit heterogeneity with possible clinical implications.
Subjects with MCI who were clinically similar showed substantial
heterogeneity in biomarkers.
Alzheimer’s disease-related plaques in
Alzheimer’s disease (AD) pathology was assessed in 587
nondemented subjects, with age at death at or more than 50 years. In 307
subjects, amyloid-β (Aβ) immunoreactive (IR) plaques were seen; in 192
subjects, neuritic plaques (NPs) stained with modified Bielschowsky silver
stain (mBky) were observed. In 20% of the whole cohort and in 62% of the 192
subjects with NPs in mBky, hyperphosphorylated tau (HPtau) IR NPs were seen. In
most cases in this nondemented cohort, the HPtau IR NPs were observed either sparsely
or to a moderate extent.
High apolipoprotein E in cerebrospinal
fluid of patients with Lewy body disorders is associated with dementia
Apolipoprotein E ε4 allele (APOE ε4) increases the
apolipoprotein E (apoE) protein levels in Alzheimer’s disease (AD)
cerebrospinal fluid (CSF). Thus, we hypothesized that apoE levels were also
associated with the APOE genotype, and amyloid-β (Aβ)-associated
clinical, functional, and imaging parameters in patients with Lewy
body-associated disorders (LBD).
The cis-regulatory effect of an
Alzheimer’s disease-associated poly-T locus on expression of TOMM40 and
apolipoprotein E genes
We investigated the genomic region spanning the Translocase of
the Outer Mitochondrial Membrane 40-kD (TOMM40)
and Apolipoprotein E (APOE)
genes, that has been associated with the risk and age of onset of late-onset
Alzheimer’s disease (LOAD) to determine whether a highly polymorphic, intronic
poly-T within this region (rs10524523; hereafter, 523) affects expression
of the APOE and TOMM40 genes. Alleles of
this locus are classified as S, short; L, long; and VL, very long based on the
number of T residues.
An 1H-MRS framework predicts
the onset of Alzheimer's disease symptoms in PSEN1 mutation carriers
Alzheimer's disease (AD) is the most common cause of dementia;
the main risk factors are age and several recently identified genes. A major
challenge for AD research is the early detection of subjects at risk. The aim
of this study is to develop a predictive model using proton magnetic resonance
spectroscopy (1H-MRS), a noninvasive technique that evaluates brain
chemistry in vivo, for monitoring the clinical outcome of carriers of a
fully penetrant mutation that causes AD.
Midlife risk score for the prediction of
dementia four decades later
The objective of this study was to obtain external validation of
the only available midlife dementia risk score cardiovascular risk factors ,
aging and dementia study (CAIDE) constituting age, education, hypertension,
obesity, and hyperlipidemia in a larger, more diverse population. Our second
aim was to improve the CAIDE risk score by additional midlife risk factors.
A phase1 study of stereotactic gene
delivery of AAV2-NGF for Alzheimer's disease
Nerve growth factor (NGF) is an endogenous neurotrophic-factor
protein with the potential to restore function and to protect degenerating
cholinergic neurons in Alzheimer's disease (AD), but safe and effective delivery
has proved unsuccessful.
This trial provides important evidence that bilateral
stereotactic administration of AAV2-NGF to the nucleus basalis of Meynert is
feasible, well-tolerated, and able to produce long-term, biologically active
NGF expression, supporting the initiation of an ongoing multicenter,
double-blind, sham-surgery-controlled trial.