An analysis of the first autopsy-confirmed case of Alzheimer’s disease (AD) in a patient previously treated with cadaver-derived human growth hormone (c-hGH) showed signs of advanced tau pathology, offering the strongest evidence to date in support of iatrogenic transmission of AD pathology, a new study suggests.

The findings, from Gargi Banerjee, PhD, and colleagues at University College London in London, England, extend the same group’s controversial 2024 report, which first described cases of suspected iatrogenic AD (iAD). That study linked early-onset dementia to exposure to c-hGH contaminated with amyloid-beta seeds, but it lacked biological evidence to confirm AD pathology and drew skepticism from some experts.

The latest report describes a postmortem examination of a male patient who received c-hGH in childhood, developed early-onset dementia at age 47, and died a decade later.

The autopsy revealed “unequivocal” neuropathologic features of AD, including extensive parenchymal amyloid-beta pathology, severe and widespread cerebral amyloid-beta angiopathy, and extensive tau pathology — “corresponding to the highest level of AD neuropathological change,” the researchers wrote.

The new findings were published online on March 30 in JAMA Neurology.

A Distinct Clinical Pattern

In 2024, the researchers reported on five people living in the UK who had been diagnosed with AD decades after receiving treatment with c-hGH derived from the pituitary glands of cadavers.

Investigators said they were the first known cases of medically acquired AD in living people. But outside experts questioned whether those cases fulfilled the complete diagnostic criteria for AD.

To extend these findings, Banerjee and colleagues conducted a detailed clinical and postmortem analysis of one of those patients and also described three other males who received c-hGH in childhood and developed dementia between the ages of 47 and 60.

Across the four cases, a notable pattern emerged: early and prominent language impairment, often resembling atypical primary progressive aphasia.

The researchers noted that such language-led presentations are rare in the general population but appeared overrepresented in this cohort. Prominent language dysfunction may represent a characteristic clinical feature of iAD, although further study is needed to confirm whether this differs from early-onset sporadic AD.

The investigators emphasized that these cases arose in the context of cadaveric tissues that are no longer used, so the findings do not mean that AD is contagious in a conventional sense.

Still, it’s “imperative that clinicians remain vigilant for cognitive symptoms in c-hGH recipients and are aware of the emerging evidence for atypical phenotypes associated with iAD,” they wrote.

Given the early age at onset, prominent language impairment, and early executive dysfunction, this syndrome could be mistaken for disorders within the frontotemporal dementia spectrum, highlighting the importance of AD biomarker testing in such patients, they noted.

Definitive Causation Elusive

In a linked editorial, Brian Appleby, MD, and Mark Cohen, MD, with Case Western Reserve University School of Medicine in Cleveland, described the new autopsy-confirmed case as “the strongest confirmation of an AD diagnosis in their cohort.”

However, current evidence “supports iatrogenic transmission of Aβ [amyloid-beta], not AD,” they cautioned.

“Neither this report nor earlier reports provide substantial evidence of iAD, and definitive causation may remain elusive given the heterogeneity of this population. However, the authors should be applauded for conducting these investigations, and such investigations should continue, given their public health implications,” Appleby and Cohen wrote.

Given that a transmission has been documented in these cases, biological evidence of Alzheimer-type neurofibrillary pathology should be “assiduously pursued,” they added.

Appleby and Cohen also emphasized that these cases do not suggest that AD is contagious or transmissible in any current medical scenario. However, recipients of c-hGH who have concerns of cognitive impairment should be formally evaluated for AD and other causes of cognitive decline, they advised.

This research had no commercial funding. Disclosure information for study authors and editorial writers is available in the original study publication.