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To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.Design: Description of a novel phenotype associated with a presenilin 1 mutation. Setting:The subject was an outpatient who was diagnosed at the local referral center.Patient: A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe ␤-amyloid (A␤) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected. Main Outcome Measures:We analyzed the processing of A␤ precursor protein in vitro as well as the A␤ species in brain tissue. Results:The PSEN1 S170F mutation induced a 3-fold increase of both secreted A␤ 42 and A␤ 40 species and a 60% increase of secreted A␤ precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated A␤ species ending at both residues 40 and 42. Conclusion:These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the A␤ aggregates' composition.

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

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