biostudies-literaturePina-Escudero SDAlzheimer&apos;s Associatione12602https://www.ebi.ac.uk/biostudies/studies/S-EPMC11262028biostudies-literatureUnknown16(3)<h4>Introduction</h4>Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.<h4>Methods</h4>We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.<h4>Results</h4>We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (<i>p</i> = 0.09). Argyrophilic grain disease was associated with atypical presentation (<i>p </i>= 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (<i>p</i> = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (<i>p</i> = 0.033).<h4>Discussion</h4>Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.<h4>Highlights</h4>Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (<i>p</i> = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (<i>p</i> = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (<i>p</i> = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (<i>p</i> = 0.033).Alzheimer's & dementia (Amsterdam, Netherlands)Comorbid neuropathology and atypical presentation of Alzheimer's disease.PMC11262028AARG‐22‐926899La Joie RRabinovici GDMiller BLGrinberg LTMundada NSHuang EJGrant HKramer JHSpina SHwang JHRosen HJGorno-Tempini MLPina-Escudero SDBoxer ALSeeley WWMiller ZAfalseComorbid neuropathology and atypical presentation of Alzheimer's disease.<h4>Introduction</h4>Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.<h4>Methods</h4>We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.<h4>Results</h4>We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (<i>p</i> = 0.09). Argyrophilic grain disease was associated with atypical presentation (<i>p </i>= 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (<i>p</i> = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (<i>p</i> = 0.033).<h4>Discussion</h4>Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.<h4>Highlights</h4>Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (<i>p</i> = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (<i>p</i> = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (<i>p</i> = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (<i>p</i> = 0.033).2024-01-01T00:00:00Z2024 Jul-Sep2025-05-18T13:26:26.178Z2025-05-18T13:26:26.178ZS-EPMC112620283904046410.1002/dad2.12602