CLINICOPATHOLOGIC EXAMINATION of human brains is the traditional starting point for our understanding of disease pathophysiology, disease treatment, and the functional-anatomical organization of the brain. In this issue of the ARCHIVES, Zarow et al1 report major cell loss in the brainstem, noradrenergic locus coeruleus (LC), in brains from patients with Alzheimer disease (AD) and Parkinson disease (PD) compared with healthy controls. The findings are, per se, not surprising as LC pathology has been previously documented in experimental and idiopathic parkinsonism.2 What is remarkable is the observation that LC neuron loss is uniformly severe across PD cases and roughly 75% of AD cases. Moreover, the degree of LC loss appears more extensive than that in 2 brain regions to which the main clinical features of AD and PD are commonly ascribed: cholinergic neurons of the nucleus basalis (AD) and dopaminergic neurons in the substantia nigra (PD). While the analysis by Zarow et al1 has several methodologic shortcomings, it is the largest single series of quantitated autopsy material from PD, AD, and control cases to be presented to date. It reemphasizes that involvement of neurochemically heterogeneous pathways by neurodegenerative diseases is likely to be the rule rather than the exception. Increasingly, the cellular pathology that is shared at a systems level, as evidenced here, is also realized at the subcellular level. Many neurodegenerative diseases ultimately derive from shared disturbances in biochemical cascades of intracellular protein trafficking.3 How these facts account for the apparent vulnerability of the LC and other neurochemically defined brain regions (eg, serotonergic dorsal raphe and cholinergic pedunculopontine nucleus, among others) in a host of neurodegenerative diseases remains unclear.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Neurology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 12
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
The Rational Clinical Examination
Among Patients With Headaches, Who Should Have Neuroimaging?
The Rational Clinical Examination
Assessing the Likelihood of a Significant Neuroimaging Intracranial Abnormality
All results at
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.