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Cerebrotendinous xanthomatosis (CTX) is an inherited disorder associated with abnormal deposition of cholestenol in the brain and other tissues. Here we report a Chinese family with two affected members of CTX. Clinical data were collected. Gene analysis, MRI, neuropsychological assessments, and the biopsy of right Achilles tendon xanthoma were carried out. The two cases had similar symptoms for cataracts, chronic diarrhea, progressive cognitive impairment and a disturbance of gait, and were identified with the same compound heterozygous mutations, c.435G>T in exon 2 and c.562C>T in exon 3. Cerebrotendinous xanthomatosis (CTX) is an inherited disorder associated with abnormal deposition of cholestenol in the brain and other tissues. Although CTX is a treatable disease, the time of beginning treatment is crucial for therapeutic effect. Unfortunately, it usually takes years even decades from initial symptoms to the diagnosis of CTX. The screening for 27-hydroxylase (CYP27A1) gene even before the occurrence of tendon xanthoma is important for early diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Synaptic degeneration is the pathologic foundation of cognitive decline in the Alzheimer's disease (AD) continuum. We aimed to determine whether cerebrospinal fluid (CSF) synaptic marker neurogranin (Ng) is a disease state or a disease stage biomarker in the AD continuum. Methods: Studies comparing CSF Ng levels among AD, mild cognitive impairment (MCI) and healthy participants were included. Studies were eligible if the correlation between CSF Ng levels and Mini-Mental Status Examination (MMSE) scores was investigated. Results: Twenty-one studies met our inclusion criteria (n = 4515). The magnitude of effect sizes was more apparent in AD (standardized mean difference [SMD] = 1.72; 95% confidence interval [CI] = 1.23–2.22), than in MCI (SMD = 0.82; 95% CI = 0.29–1.34) compared to control populations. These results suggest that CSF Ng can discriminate AD and MCI from control populations, implying that synaptic degeneration worsens as patients progress from MCI to AD. However, there was a very weak correlation between CSF Ng levels and MMSE scores (r = −0.15; 95% CI = −0.21–-0.08) among the whole populations, suggesting that an increment of CSF Ng is best considered a biological evidence of disease state in the AD continuum. Conclusion: Our study provides evidence that the synaptic marker CSF Ng can be used as a disease state biomarker for the AD continuum. Because synaptic degeneration is a distinct pathologic event from amyloid deposition and neurofibrillary tangle formation, CSF Ng may provide an important supplementation to the AT(N) biomarker system to reveal the sequence of neuropathology. [ABSTRACT FROM AUTHOR]

X-linked adrenoleukodystrophy is an inherited disease caused by abnormal accumulation of very long chain fatty acids. The diagnosis of X-linked adrenoleukodystrophy can be confirmed with the mutation of ABCD1 gene. The main symptom of the X-linked adrenoleukodystrophy is spastic paraparesis, and autonomic dysfunction is rare in X-linked adrenoleukodystrophy. Here, we presented an X-ALD case of a 46-year-old Asian male with severe autonomic dysfunction. Impairment of the autonomic nervous system may closely relate to mitochondrial defect. [ABSTRACT FROM AUTHOR]

Melatonin plays an important role in aging and relevant neurodegeneration as an antioxidant and neuroprotector. It can interact with β-amyloid (Aβ) generation, inhibit formation of β-sheet and amyloid fibrils, modulate apoptosis, and protect cholinergic system function in Alzheimer's disease animal model. Recently, its effects on anesthetic-induced neurodegeneration have received more attention, and in this investigation, we explored whether melatonin can attenuate Aβ1-40 generation and cholinergic dysfunction in the hippocampus of aged rats induced by isoflurane through enzyme-linked immunosorbent assay, Western blot, immunohistochemistry, and immunofluorescence. The results showed that isoflurane increased Aβ1-40 generation and caused cholinergic dysfunction through decreasing choline acetyltransferase (ChAT) expression in the hippocampus in a dose-dependent way, and intraperitoneal melatonin premedication attenuated the neurodegeneration through inhibiting Aβ1-40 generation and increasing ChAT expression, and its effects were more obvious in high-concentration isoflurane group. Collectively, our results provide evidence for the therapeutic value of melatonin on isoflurane-induced neurodegeneration, including Aβ1-40 generation and cholinergic dysfunction, and further work is necessary to clarify its target sites and detailed mechanisms. [ABSTRACT FROM AUTHOR]