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  • Title: Alzheimer disease pathology in amyotrophic lateral sclerosis.
    Author: Hamilton RL, Bowser R.
    Journal: Acta Neuropathol; 2004 Jun; 107(6):515-22. PubMed ID: 15024584.
    Abstract:
    Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons. In some ALS patients, dementia or aphasia may be present (ALS-D). The dementia is most commonly a frontotemporal dementia (FTD), and many of these cases have ubiquitin-positive, tau-negative inclusions in neurons of the dentate gyrus and superficial layers of the frontal and temporal lobes. Identical inclusions have been found in cases presenting with FTD and have been designated motor neuron disease (MND)-inclusions. Cases of ALS-D without MND-inclusions have been reported to show neocortical gliosis, neuronal loss, and superficial spongiosis, but there have also been scattered case reports of ALS with Alzheimer's disease (AD). To determine whether AD pathology may play a role in the dementia or aphasia syndromes in ALS, we reviewed 30 cases of sporadic ALS diagnosed at the University of Pittsburgh Medical Center. A clinical history of ALS-D was found in 24.1% of the cases, of which 57% had MND-inclusions. Although the ALS-D cases with MND-inclusions typically had amyloid-beta (Abeta) plaques, there were no neuritic plaques. Three cases of ALS-D had no MND-inclusions, and two of these fulfilled pathological criteria for AD. One ALS-D case showed severe amyloid angiopathy but no neuritic plaques or MND-inclusions. MND-inclusions were not found in any ALS case without dementia; however, four patients without dementia or aphasia showed moderate or frequent numbers of neuritic plaques. In conclusion, we found that approximately 30% of ALS cases with dementia have AD and that some ALS cases without frank dementia have significant AD pathology.
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